f 


■>i.' 


LIBRARY 

OF  THE 

University  of  California. 


Class 


TEXT  BOOK 


OF 


COMPARATIVE 

GENERAL  PATHOLOGY 


FOR 


Practitioners  and  Students  of  Veterinary  Medicine 

BY 

PROFESSOR  DR.  TH.  KITT 

OF  MUNICH 


Authorized  Translation 

BY 

DR.  WILLIAM  W.  CADBURY 

Assistant  Demonstrator  of  Patholog:>'  in  the  Universitj'  of  Pennsylvania 


Edited  with  Notes  and  Additional  Illustrations 

BY 

DR.  ALLEN  J.  SMITH 

Professor  of  Pathology  in  the  University  of  Pennsylvania 


Illustrated  with  Four  Colored  Plates  and  One  Hundred  and 
Thirty-one  Text  Illustrations 


V"  OF  THE 

UNIVERSITY 

OF  y  CHICAGO 

CAvro^^}^^    W.  T.  KEENER  &  CO. 

1 906 


.^^ 


*V\., 


<d' 


ff 


SEVERAL 


Copyrighted,   1906 
Bv  W.  T.  Keener 


PREFACE    TO    GERMAN    EDITION 

The  introduction  of  students  of  veterinary  medicine  to  the 
study  of  pathology,  because  of  the  lack  up  to  the  present  time  of 
a  German  text  book  of  general  pathology  adapted  to  diseases 
of  animals,  has  depended  chiefly  upon  works  written  for  the 
practitioner  of  human  medicine;  the  lectures  of  instructors  in  vet- 
erinary medicine  and  students'  notes,  made  with  more  or  less 
accuracy,  supplying  the  necessary  additions  and  explanations. 

Only  one  work,  the  Text  Book  of  General  Pathological  Anat- 
omy by  Birch-Hirschfeld,  has  been  amended  from  the  standpoint 
of  our  special  branch  of  medicine,  by  the  addition  of  veterinary- 
medical  paragraphs  from  the  facile  pen  of  Johne,  so  as  to  seem 
adapted  for  students  in  veterinary  schools ;  but  it  is  confined  to 
pathological  anatomy,  and  the  physiological  and  setiological  fea- 
tures, the  manifestation  of  functional  impairments,  pathogenesis, 
etc.,  require  further  reference  to  special  works. 

As  an  introduction  and  foundation  for  appreciation  of  the 
practice  of  veterinary  medicine,  to  be  studied,  and  put  into  applica- 
tion in  the  latter  portions  of  the  college  curriculum,  after  com- 
pletion of  the  courses  in  anatomy,  physiology  and  the  natural 
sciences,  the  student  should  be  given  a  general  idea  of  the  mean- 
ing of  disease,  the  aetiology  of  diseases,  of  the  make-up  of  our 
medical  knowledge  and  of  the  principles  of  classification,  as  well 
as  a  general  familiarity  with  the  alterations  in  structure  and  func- 
tion met  in  disease.  It  is  for  this  reason  that  lectures  on  general 
pathology  are  provided,  introductory  to  the  special  applied 
branches  of  study.  The  need  of  a  work  concisely  comprehending 
such  features  has  determined  me  tO'  undertake  the  task  of  pre- 
paring a  condensed  outline  of  the  fundamental  facts  of  pathology 
with  special  adaptations  to  the  requirements  of  veterinarians.  Of 
course,  it  has  been  necessary  to. make  use  of  much  material  from 
works  intended  for  the  student  of  human  medicine,  and  I  am 
vividly  reminded  of  the  old  sentence  in  the  Latin  grammar — "Plinius 


iv  Preface  to  German  Edition. 

nullum  librum  legit,  ex  quo  noii  excerpserit."  I  therefore  ac- 
knowledge at  the  outset  and  at  various  places  in  the  text,  that  I 
have  freely  employed  in  the  preparation  of  the  following  text- 
book the  works  of  Ribbert,  Perls,  Krehl,  Durk,  Samuel,  Thoma, 
Birsch-Hirschfeld,  Johne,  Uhle  and  Wagner,  as  it  is  in  fact  prac- 
tically impossible  to  write  an  authoritative  work  on  general 
pathology  without  dependence  upon  other  authors. 

The  scientific  development  of  veterinary  medicine  depends 
primarily  upon  the  same  principles  which  obtain  in  human  med- 
icine. The  propositions  and  methods  of  research  which  were 
originally  employed  in  the  study  of  human  pathology,  are  for  us, 
too,  fundamentals  for  the  appreciation  and  investigation  of  the 
nature  of  the  animal  diseases.  Every  new  advance  in  human 
medicine  in  the  fields  of  anatomy,  physiology,  the  use  of  the  micro- 
scope, technique  of  clinical  study,  surgical  and  therapeutic  meth- 
ods, bacteriological  and  practical  hygiene,  has  been  of  advantage 
to  comparative  medicine,  and,  mutatis  mutandis,  has  found  an 
application  in  veterinary  practice,  and  has  pointed  out  the  way 
for  advanced  work  in  our  own  branch.  There  has  been  much  as- 
sistance afforded,  too,  in  the  fact  that  many  of  the  discoveries 
of  value  to  human  medicine  have  been  made  from  experimental 
studies  upon  animals,  and  the  principles  of  general  pathology  par- 
ticularly have  been  fundamentally  proven  by  comparative  study 
of  the  anatomy  and  physiology  of  animals;  both  branches  of  med- 
icine, therefore,  drawing  from  the  same  sources  and  having  a 
common  field  of  work. 

Apart  from  these  considerations,  however,  the  representatives 
of  veterinary  medicine  have,  by  their  independent  achievements, 
built  up  the  pillars  and  walls  of  their  own  scientific  temple,  wdth 
such  multiplicity  of  specialized  purposes  and  requirements  that 
the  method  and  practice  of  veterinars'  medical  instruction  have 
come  to  have  a  peculiar  character  of  their  own.  Consideration 
of  these  requirements  is  attempted  in  this  volume. 

It  is  well  known  to  every  teacher  who  is  required  to  act  as 
an  examiner,  how  difficult  it  often  is  for  the  candidates  in  an 
examination  to  express  what  they  well  know  and  how,  no  matter 
how  clearly  the  questions  may  be  presented,  or  what  statements 
are  made  suggesting  a  proper  answer,  this  or  that  really  capable 
student  finds  himself  forced  to  struggle  with  words  and  is  handi- 
capped in  expressing  his  ideas.  In  order  to  lessen  these  diffi- 
culties  for  students,   I  have   endeavored  to    frame    mv  definitions 


Preface  to  German  Edition.  v 

concisely,  to  present  the  positive  facts  in  as  clear  and  as  brief 
a  manner  as  possible,  and  to  limit  to  what  is  absolutely  essential 
the  incomplete,  uncertain  and  controversial  points  of  study,  the 
elaborate  discussion  of  which  is  usually  confusing  and  tends  to 
weary  the  student.  Of  course,  important  objections  and  ques- 
tioned points  in  theories  have  been  noticed,  lest  the  student  be 
led  to  luere  memorization  and  superficial  study,  and  in  order  that  he 
may  be  stimulated  to  think.  I  believe  that  the  work  will  be  found 
useful  to  the  practising-  veterinarian  as  well,  as  a  general  presenta- 
tion of  the  most  recent  position  of  the  science. 

I  have  omitted  description  of  the  individual  types  of  animal 
parasites  and  bacteria  and  taken  up  only  in  this  connection  their 
bearings  upon  general  pathology.  The  scope  of  the  v/ork  would 
otherwise  have  been  too  large;  and  full  details  upon  these  sub- 
jects may  be  found  in  the  part  devoted  to  special  pathology 
{Lehrhuch  der  pathol.  Anatomic  der  Haitsticrc.  II.  Aufl.  1901. 
F.  Enke,  Stuttgart)  and  in  my  Lehrhuch  der  Bakterienkunde  und 
pathol  Mikroskopie  (IV.  Aufl.  M.  Perles,  Wien,  1903).  The 
subject  of  malformations  is  also  treated  of  at  the  beginning  of  the 
special  section  just  mentioned,  and  a  repetition  is  therefore  super- 
fluous. 

The  publisher  has  presented  the  volume  in  an  excellence  of 
style  which  places  me  under  special  obligation  to  him. 

Numerous  new  illustrations  are  included,  prepared  by  the  ar- 
tistic hand  of  K.  Dirr;  some  of  the  cuts  I  have  borrowed  from 
the  works  of  authors  cited  in  the  text.  For  a  mmiber  of  photo- 
graphs I  must  thank  for  their  kindness  the  veterinary  physicians 
Dr.  Jakob  and  Dr.  W.  Ernst,  the  latter  of  whom,  a  skillful  micro- 
scopist  and  bacteriologist,  has  been  engaged  for  a  number  of 
years  in  my  institution  and  has  aided  me  in  a  most  valuable  man- 
ner in  carrying  on  investigations  bearing  upon  my  studies. 

Munich.  TH.  KITT. 


PREFACE   TO    AMERICAN    EDITION 

The  work  of  translating  and  preparing  for  publication  the 
following  edition  of  Kitt's  General  Pathology  has  been  a  pleasure, 
because  of  the  real  value  of  the  work  and  because  both  editor  and 
translator  have  believed  the  labor  a  service  to  the  profession.  As 
Professor  Kitt  states  in  the  preface  to  the  German  edition,  it  is 
practically  the  only  work  devoted  to  a  discussion  of  general 
pathology  from  the  standpoint  of  the  veterinarian ;  and  the  need 
of  such  a  work  has  long  been  manifest  to  every  teacher  of  pathol- 
ogy in  charge  of  students  of  veterinary  medicine.  The  impres- 
sions given  by  any  book  upon  pathology,  even  the  best,  which  has 
been  framed  primarily  for  use  in  connection  with  human  medicine, 
are  often  unfortunate  from  the  inaptness  of  the  descriptions  of 
lesions  for  the  needs  of  men  studying  comparative  medicine.  It  is 
undoubtedly  true  that  the  general  processes  of  disease  are  funda- 
mentally the  same  in  whatever  subject  they  occur;  but  the 
varieties  of  appearances  of  one  and  the  same  type  of  lesion  in 
different  species  may  well  be  sufficiently  marked  to  make  the 
descriptions  based  upon  the  changes  met  in  any  given  animal 
confusing  and  perhaps  inadequate  for  students,  whose  experience 
in  the  earlier  years  is  anything  but  extensive.  The  differences, 
for  example,  in  the  appearances  of  a  tuberculous  caseated  area  in 
man,  in  the  cow,  hog,  horse,  or  in  carnivora,  well  illustrate  the 
point  in  mind;  or  the  differences  in  bulk  and  in  other  character- 
istics of  various  tumors  as  met  in  man  and  in  the  large  domestic 
animals  serve  as  an  example.  The  adaptation  of  the  present 
volume  to  the  needs  of  students  who,  as  Professor  Kitt  points 
out,  have  had  to  accept,  as  a  rule,  the  descriptions  of  lesions  as 
seen  in  man  and  then  amend  them  by  notes  from  lectures,  has 
strongly  appealed  to  us  as  instructors  of  veterinary  students,  and 
will  find,  w.e  believe,  an  equal  appreciation  from  others  whose 
work  has  fallen  in  similar  lines. 

The   book   reflects   well   the   tendency   of   modern   pathological 


viii  Preface  to  American  Edition. 

teaching  to  devote  considerable  effort  to  direct  the  thought  of  the 
reader  along  lines  of  pathological  physiology,  to  make  the  student 
reason  for  himself  from  given  anatomical  data  and  appearances 
as  to  the  necessary  functional  faults  and  failures  which  would 
follow.  Pathological  anatomy  is,  of  course,  fundamental  and 
finds  its  place  on  every  page ;  but  the  author  has  had  in  mind 
the  application  of  pathology  to  the  living  diseased  animal,  and 
the  anatomical  descriptions  and  discussions  serve  as  a  basis  for 
explanation  of  the  development  of  the  processes  and  the  func- 
tional faults  the  diseased  animal  must  necessarily  manifest.  The 
chapters  on  disturbances  of  the  circulatory,  respiratory  and  other 
functions  are,  of  course,  brief,  but  they  are  by  no  means  super- 
ficial and  indicate  well  the  lines  of  necessary  study  for  the  prac- 
ticing physician  and  are  stimulative  to  thought  on  the  part  of 
the  student. 

The  value  of  such  a  work  is  not  confined  to  the  veterinarian ; 
the  intimate  relations  comparative  pathology  bears  to  the  study  of 
human  medicine  and  the  need  that  experimentalists  should  be  in 
the  best  possible  position  to  appreciate  the  reactions  peculiar  to 
various  species  of  experiment  animals  require  of  pathologists 
broader  and  broader  powers  of  recognition.  Much  of  the  criticism 
against  animal  experimentation  has  its  only  force  in  that  in  the 
hands  of  men  unfamiliar  with  the  animals  utilized,  both  in  their 
normal  life  and  in  their  pathological  reactions,  the  best  results 
are  not  obtained,  at  least  not  appreciated,  by  such  workers  in 
return  for  the  sacrifice  entailed.  The  best  is  accomplished,  other 
things  being  equal,  by  men  whose  training  comprehends  a  broad 
biological  and  physiological  experience  and  who  are  familiar  with 
the  peculiarities  of  physiological  reaction  and  anatomical  changes 
to  be  met  in  the  animals  employed  under  the  operation  of  given 
pathogenic  influences.  Such  works  as  the  present  volume,  intro- 
ductory to  the  fuller  Special  Pathology  in  the  companion  volumes 
of  the  German  edition,  have  therefore  a  proper  place  on  the 
shelves  of  every  pathologist,  whether  his  work  deals  with  human 
or  with  comparative  problems  as  its  major  field. 

In  presenting  the  book  to  our  English-speaking  colleagues  and 
students,  .the  editor  and  translator  have  endeavored  to  follow 
closely  Professor  Kitt's  language,  although  no  attempt  to  be  abso- 
lutely literal  in  the  translation  has  been  made.  Doubtless  the 
effort  to  translate  the  German  idiom  to  its  English  equivalent  has 
often  failed ;  and  we  both  appreciate  the  fact  that  unwittingly  the 


Preface  to  American  Edition.  ix 

verbiage  of  the  translation  has  sometimes,  in  the  endeavor  to  keep 
close  to  the  original,  come  to  be  somewhat  complicated  for  English 
text.  The  editorial  notes,  which  are  always  enclosed  in  special 
brackets  ([  ]),  have  purposely  been  kept  within  brief  limits, 
because  of  our  realization  of  the  sufficiency  of  the  work  for  the 
introductory  purposes  for  which  it  is  intended  by  the  author,  and 
because  of  a  desire  to  keep  the  size  of  the  book  near  the  limits 
of  the  original  edition.  We  feel  that  for  use  at  the  hands  of 
graduate  physicians  the  book  as  it  stands  meets  the  purpose  for 
which  it  was  written ;  for  student  purposes,  as  a  handbook  as 
well  as  a  general  text,  it  would  perhaps  have  been  regarded  as 
an  advantage  to  have  added  descriptive  matter  to  the  tables  of 
the  vegetable  and  animal  parasitic  organisms  and  to  have  ex- 
panded the  text  somewhat  in  connection  with  minute  anatomy, 
thus  giving  it  a  fuller  adaptation  to  laboratory  studies.  A  num- 
ber of  illustrations  have  been  generously  added  by  the  publishers 
with  this  latter  view  in  mind.  These  illustrations,  made  by  the 
well-known  artist,  Louis  Schmidt,  include  figures  63,  82,  86,  89, 
91,  97,  loi,  102,  103,  104,  III  and  125;  and  it  is  thought  that 
the  book,  with  such  additions,  will  find  a  fuller  place  as  an  aid  to 
the  student  in  the  laboratory  of  pathological  histology. 

The  publishers  have  not  spared  expense  to  make  this  work 
possible  in  the  translated  form,  and  by  their  interest  have,  we 
feel,  placed  the  profession  under  obligations.  For  ourselves  the 
venture  is  in  no  sense  a  financial  one,  and  if  others  will  find,  as 
we  hope,  that  our  efforts  have  aided  in  pressing  forward  the 
general  good  for  both  veterinary  and  human  medicine,  our  com- 
pensation will  be  ample. 

Allen  J.  Smith. 
William   W.   Cadbury. 

September,   1906. 


TABLE    OF   CONTENTS 


PAGE 

Preface  to  German  Edition iii 

Preface  to  American  Edition vii 

Introduction    i 

Definition  of  Patholog}' ;  Conceptions  of  Disease ;  Pro- 
cesses of  Disease. 

History   of   Pathology lo 

Disposition   Toward  Disease i6 

Predisposition  and  Immunity ;  Defensive  Mechanisms 
of  the  Body. 

Congenital  and  Inherited  Disease 30 

Placental,  Intrauterine  Origin  of  Disease;  Germinal 
Variation ;  Germinative  Predisposition ;  Hereditary 
Conditions. 

Causes  of  Disease ' 35 

Disturbances  of  Nutrition  and  Alimentation 36 

Respiratory   Disturbances 38 

Excessive  Functional  Activity .  .  . ". 40 

Thermic    Influences 41 

Chilling- 45 

Electrical  Agencies 48 

Mechanical  and  Traumatic  Agencies 49 

Chemical  or  Toxic  Agents 50 

Microbic  or  Infectious  Agents 54 

Animal    Parasites 76 

Course  and  Termination  of  Disease 91 

Symptoms,  Diagnosis,  Natural  and  x\rtificial  ]Means  of 
Recovery,  Death. 

Circulatory  Disturbances 106 

Disturbance;^  of  Cardiac  Efficiency 106 

Local  Variations  in  Amount  of  Blood  in  a  part   (Hy-. 

persemia,  Anaemia) 109 


xii  Table  of  Contents. 

PAGE 

Haemorrhage 119 

Dropsy  and  CEdenia 

Occlusion   of   Blood  Vessels    (Thrombosis   and   Embo- 
lism)   

Alterations    of    the    Blood     (Plethora,    the    xA.ngemias, 
Leukaemia) 156 

Disturbances  of  Metabolism,  Retrograde  Changes  and  Necrotic 

Processes 165 

Disturbances  of  Heat  Regulation,  Overheating,  Fever.  165 

Necrosis 1 76 

Atrophy 185 

Cloudy    Swelling 190 

The  Fatty  Changes 192 

Hyaline  Degeneration 199 

Mucoid    Degeneration 202 

Colloid    Degeneration 204 

Glycogenic  Infiltration 20s 

Amyloid  Degeneration 205 

Pigmentation 209 

Calcification  and  Concrement   Formation 216 

Processes  of  Repair  and  New  Formation 232 

Regeneration 232 

Transplantation 25 1 

Hypertrophy 254 

Inflammation 258 

Tuberculosis 291 

Glanders 311 

Actinomycosis 318 

Botryomycosis 324 

Tumors    ( Autoblastomata) 325 

Fibroma  (p.  :^4i)^Lipoiiia  (p.  346) — Myxoma  (p. 
349) — Cliondroma  (p.  350) — Osteoma  (p.  353) — 
Myoma  (p.  356) — Neuroma,  Glioma  (p.  358) — Hccm- 
angioma,  Lymphangio'ma  (p.  362) — Sarcoma  (p.  365) 
— Lymp/ioma  (p.  372) — Melanoma  (p.  ^yy) — Eiido-, 
Peri-thelioma.  CJwIesteoma  (p.  380) — Papilloma  (p. 
383) — Adenoma  (p.  388) — Cancers  (p.  394) — Epithe- 
lial Cysts,  Dermoid  Cysts  (p.  415) — Adenocystoma  (p. 
418) — Odontoma  (p.  419) — Teratoma.  Embryoma  (p. 
421). 


Tabic  of  Contents.  xiii 

PAGE 

Functional    Disturbances 423 

Nervous  Disturbances;   Disturbances  of  Motion 423 

Digestive   Disturbances 436 

Respiratory    Disturbances 448 

Disturbances  of  Urinary   Excretion 454 

Disturbances  of  the  Thyroid   Function 459 

Disturbances  of  the  Sexual   Function 461 

Disturbances  of  the  Cutaneous    Function 462 

Index 465 


.■af 


INTRODUCTION 

Pathology  (t6  7rd6'os,  suffering;  6  x670s,  science)  may  he  defined 
as  the  natural  history  of  diseases,  or  as  the  scientiHc  study 
of  diseases.  The  terms  "disease,"  "disordered"  and  "morbid"  are 
employed  to  indicate  the  existence  of  disturbances  of  the  physio- 
logical activity  of  the  organs;  that  is,  the  presence  of  some  devia- 
tion from  the  anatomical  and  chemical  relations  of  the  body- 
constituents  which  exceeds  the  limits  of  physiological  variation  and 
which  calls  forth  such  disturbances. 

In  ordinary  life  we  designate  as  "health"  a  state  of  the  body  in 
which  the  vital  manifestations  (nutrition,  metabolism,  motility,  sen- 
sation, psychical  activity)  are  carried  on  in  harmony;  and  it  is  as- 
sumed in  addition  that  the  various  organs  are  of  normal  structure, 
and  that  the  individual  experiences  a  feeling  of  well-being.  On 
the  other  hand  the  term  "disease"  carries  with  it  a  conception 
opposed  to  this  so-called  health,  that  of  an  irregularity  of  function 
and  of  impairment  of  efficiency  of  the  organs  and  systems  of 
organs,  accompanied  as  a  rule  by  a  feeling  of  discomfort. 

The  distinctions  between  these  two  conceptions  merge,  however, 
and  are  lost  when  we  consider  the  infinite  gradations  between  health 
and  disease,  and  as  we  are  required  to  employ  the  terms,  either 
empirically  or  scientifically,  in  a  narrower  or  broader  sense.  There 
might  exist,  for  example,  an  organ  of  distinctly  faulty  structure  in 
an  individual  without  causing  any  appreciable  disturbance  of  the 
general  health,  as  a  malformed  kidney,  or  a  curvature  of  the  spine. 
One  of  two  paired  organs,  as  a  lobe  of  the  thyroid  or  one  of  the 
kidneys,  may  be  anatomically  so  altered  and  incapable  o£.  function 
as  to  merit  being  considered  diseased ;  nevertheless  the  individual 
may  feel  well  and  live  many  years.  Moreover  in  healthy  bodies 
there  mav  now  and  again  be  evinced  deviations  from  the  normal 
vital  manifestations  which  may  simulate  morbid  disturbances,  but 
which  are  not  felt  or  regarded  as  such  because  of  their  brief  dura- 
tion, because  they  are  soon  corrected  by  the  protective  and  regu- 
lating mechanism  of  the  body,  or  are  at  most  expressions  of  such 


2  IiitroducfioiL 

adjustments;  for  example,  after  marching  there  may  be  a  brief 
elevation  of  body  temperature  even  to  fever  heat.  In  considering  a 
body  corpulent  from  fat  deposit,  one  may  be  at  a  loss  to  indicate 
whether  the  corpulence  is  but  a  normal  condition,  or  whether  a 
really  morbid  state  of  obesity  has  commenced ;  and,  at  least  in  the 
popular  mind,  intoxication  from  alcohol  is  certainly  not  to  be  con- 
sidered as  a  disease  although  in  the  stricter  interpretation  we  are 
forced  to  look  upon  it  as  a  departure  from  the  state  of  health. 

Besides  the  term  Disease,  therefore,  general  convenience  of 
speech  requires  the  use  of  such  terms  as  Sickness,  Indisposition, 
Feeble  Health,  Defect,  Fault  or  Damage,  and  limits  the  employ- 
ment of  "disease"'  to  such  conditions  in  which  the  structural  and 
functional  disturbances  go  so  far  as  to  hinder  the  more  important 
vital  processes,  to  cause  pain  and  to  impair  in  an  essential  manner 
the  vital  phenomena  of  the  organism  as  a  whole.  By  the  expressions 
"feeble  health,"  "debility"  (imbeciUitas)  is  to  be  understood  a 
diminished  power  of  bodily  resistance  to  pathogenic  influences ; 
"sickness"  or  "indisposition"  is  used  when  there  is  a  subjective 
feeling  of  impaired  health  and  where  but  minor  grades  of  disease 
actually  exist.  "Defects,"  "damages"  and  "faults"  are  conditions  in 
which  certain  parts  of  the  body  appear  structurally  abnormal  and 
do  not  properly  functionate ;  conditions  in  which  the  derangements 
have  come  to  a  definite  standstill,  and  only  under  special  conditions 
are  likely  to  give  rise  to  further  morbid  manifestations.  Should 
these  be  congenital,  arising  in  the  period  of  foetal  life,  they  are 
spoken  of  as  Malformations,  Congenital  Defects,  Developmental 
Faults,  Vitia  Congenita;  if  acquired  after  birth  as  sequels  of  dis- 
ease (wholly  or  partly  removed),  or  if  the  results  of  mechanical  in- 
fluences, as  Acquired  Deformities,  Mutilations,  or  Vitia  Acquisita. 

In  its  proper  meaning  the  term  Disease  has  no  reference  to  any 
entity  or  thing,  but  to  more  or  less  complicated  processes  and  con- 
ditions which  are  evidences  of  disturbances  of  the  physiological 
constitution  and  activity  of  the  body ;  this  applying  to  the  individual 
cells  as  well  as  to  the  whole  group  of  cells  making  up  the  organism. 
Diseases  are  therefore  to  be  distinguished  as  diseases  of  the  cells 
or  structural  elements  of  the  organs,  as  diseases  of  the  tissues, 
of  organs,  of  systems,  and  of  the  individual  or  organism  as  a  whole. 
[Inasmuch  as  life  is  but  an  expression  of  a  harmony  of  structural 
and  functional  relation  between  the  cellular  constituents  of  the  body 
among  themselves  and  of  the  maintenance  of  efficient  adaptability  to 
the  bodilv  environment,  disease  should  be  thought  of  as  being  made 


Nature  of  Disease.  3 

up  of  anv  chang-e  of  structure  or  modification  of  function  which 
may  impaii'  this  harmony  and  adaptabiUty  to  cellular  or  bodily 
surroundings.  And  individual  diseases  may  then  be  understood  as 
including-  special  groups  of  such  modifications  of  structure  and 
function,  these  groups  varying  in  the  isolated  afifections  in  type, 
distribution  and  number.]  The  processes  which  go  to  make 
up  a  disease  are  not  fundamentally  dififerent  from  the  physiological 
processes,  are  not  features  foreign  to  the  operation  and  structure 
of  the  healthv  bodv.  but  are  to  be  directly  referred  to  these ;  the  only 
difference  being  that  in  disease  they  manifest  themselves  in  a  site, 
at  a  time  or  in  a  degree  other  than  in  the  normal  state  of  the  body. 
Pathological  processes  may  therefore,  as  by  Mrchow,  be  con- 
sidered as  heterotopic,  heterochronic  and  heterouictric  physiologi- 
cal processes  (^repos,  another;  3  T6iros,  place;  xp^^o'^^  time;  /x^rpov, 
amount).  As  an  illustration:  a  h?emorrhage  into  the  ovary,  caused 
by  the  bursting  of  a  follicle  and  ovulation,  is  normal,  but  a 
haemorrhage  into  the  brain  is  abnormal ;  unconsciousness  in  sleep 
is  normal,  but  at  an  unusual  time  and  in  pronounced  degree,  as  in 
swooning,  is  pathological.  Almost  invariably  physiological  ana- 
logies are  to  be  found,  in  comparison  with  which  the  alterations  of 
disease  are  manifestly  but  quantitative  variations  or  variations  of 
place  and  time.  The  gastric  mucous  membrane,  when  the  stomach 
is  full  and  engorged  during  the  process  of  digestion,  is  very  full  of 
blood  and  red ;  in  another  part  of  the  body,  as  the  conjunctival 
mucous  membrane,  this  same  redness  and  congestion  would  be 
pathological.  The  endometrium  normally  sheds  epithelial  cells  and 
leucocytes  in  the  lochial  secretion  in  considerable  numbers  after  the 
removal  of  the  placenta ;  were  this  not  merely  temporary  but  of  per- 
manent duration  the  condition  would  constitute  a  pathological  one, 
a  catarrh.  In  the  tumors  or  pathological  new  growths,  which  are 
apparently  so  foreign  to  the  general  organism,  there  are  to  be  found 
only  the  same  tissue  elements  as  belong  to  the  normal  body,  which 
however  possess  a  power  of  growth  which  is  abnormal.  Even  the 
phenomena  of  death  have  their  physiological  counterpart,  as  in  the 
mummification  of  the  umbilical  cord. 

The  various  pathological  processes  may  be  classed  as  follows : 
(i)  Anatomical-pathological  processes  (gross  pathological-ana- 
tomical or  pathological-histological)  :  Here  are  included  all 
changes  of  structure  or  lesions  whether  of  the  gross  organs  or 
of  the  tissues  and  cells,  as  lesions  of  continuity  of  the  skin  and 
musculature  (wounds),  changes  in  consistence  (as  cerebral  soften- 


4  Introduction. 

ing  or  induration  of  the  liver),  occupation  of  spaces  and  formation 
of  false  membranes  by  fibrinous  material  (pleurisy,  croup),  micro- 
scopic changes  in  the  cells  (karyolysis,  fatty  infiltration). 
(2)  Chemico-pathological  processes:  Quantitative  and  qualitative 
changes  of  the  chemical  constituents  of  the  animal  organism  and  its 
parts  (metabolic  faults),  as  the  presence  of  bile  in  the  blood,  albu- 
men in  the  urine,  uric  acid  in  the  joints  or  abnormal  proportion  of 
water  in  the  blood.  [Here  might  well  be  included,  too,  the  ex- 
cessive formation  or  uric  acid  or  its  salts,  of  the  faulty  carbohy- 
drate changes  of  diabetes,  the  development  of  faulty  types  of 
albumen  in  the  blood  and  within  the  cells,  the  toxic  changes  of 
uraemia  and  other  intoxications,  those  essentially  chemical  processes 
which  underlie  in  an  important  degree  the  changes  produced  by 
infections,  as  well  as  a  wide  group  of  more  or  less  indefinite  meta- 
bolic diseases.] 

(3)  Functional-pathological  or  symptomatic  disturbances  (some- 
times spoken  of  as  dynamic  disturbances)  :  These  are  faults  in  the 
nicety  of  balance  of  the  various  physiological  activities  of  the  or- 
ganism, as  the  occurrence  of  convulsions,  pain,  unconsciousness, 
labored  breathing,  diarrhoea  or  dribbling  urine.  Functional  dis- 
turbances are  usually  caused  by  structural  and  metabolic  faults. 
Commonly  the  latter  are  primary,  as  in  physiological  life  the  effi- 
ciency, growth  and  development  of  the  organs  are  dependent  upon 
the  chemical  processes  of  nutrition  and  metabolism.  Our  knowl- 
edge of  the  morphological  and  chemical  basis  of  functional  de- 
rangements is,  however,  incomplete. 

Consideration,  description  and  investigation  of  pathological 
variations  may  therefore  be  divided  into  (a)  Pathological  Morphology 
or  Anatomy,  (b)  Pathological  Chemistry  and  (c)  Symptomatology, 
together  with  (d)  considerations  of  the  influences  under  which  dis- 
eases develop,  and  the  actual  causes  of  disease  (Aetiology:  ahia, 
cause).  In  the  origin  of  disease  some  cause  is  apt  to  act  so  as  to 
bring  about  material  changes,  chemical  and  physical,  patholo^^ical 
lesions  {Iced ere,  to  injure)  of  the  component  elements  and  organs, 
as  well  as  the  counteraction  or  pathological  reaction  on  the  part 
of  these  same  elements  and  organs,  both  of  which  manifest  them- 
selves by  functional  disturbances   (symptoms  or  signs  of  disease). 

That  phase  of  pathology  which  seeks  to  explain  the  development 
of  lesions  and  symptoms  constitutes  Pathogenesis  (7;  yheais,  de- 
velopment, beginning)  ;  that  which  concerns  the  observation  of 
the   chronological    succession   of   disease-events,  the   onset,    course 


Divisions  of  Pathology^  5 

aiul  termination  of  disease,  is  known  as  Nosology  (  ^  vdaos,  sick- 
ness). 

The  object  of  pathology  is  primarily  the  acquisition  of  knowl- 
edge of  the  laws  which  govern  pathological  changes  (Pafhognomy, 
from  yiyvwcTKU},  to  becomc  acquainted  with)  ;  in  addition,  to  point 
how  and  why  certain  lesions  and  reaction^  must  follow  certain 
causes.  Dealing  in  its  broadest  sense  with  life  under  abnormal  con- 
ditions, pathology  presents  itself  as  Pathological  Physiology ;  and 
moreover  provides  a  scientific  basis  for  the  prevention  and  cure  of 
disease,  and  thus  the  foundation  of  rational  Prophylaxis  (irpo- 
(pvXdaaw,  to  prevent  or  guard  against  something)  and  Therapy 
i]  eepaireia,  therapcutics,   from   depaweiiw,  to  attend,  to  heal). 

For  convenience  in  instruction  pathology  is  separated  into  two 
divisions :  General  Pathology  and  Special  Pathology.  This  is  done 
with  the  purpose  of  facilitating  a  systematic  presentation  of  the 
wide  scope  of  the  study;  general  pathology  dealing  with  the  ele- 
mentary pathological  processes  and  their  causes  without  reference 
to  their  site  in  the  body,  and  being  thus  introductory  to  special 
pathology,  in  which  the  various  individual  phenomena  of  morbid 
change  in  the  different  organs  and  systems  find  expression. 

With  the  healthy  living  individual  as  its  starting  point,  and  basing 
its  comparisons  upon  the  average  normal  structure  and  ordinary 
physiological  functions  of  the  organism,  pathology  is  dependent 
upon  anatomy,  physiology,  chemistry  and  physics  as  its  guides.  A 
clear  understanding  or  comprehension  of  its  processes  is  impossible 
without  a  thorough  knowledge  of  the  organization  of  the  animal 
body;  a  knowledge  which  includes  the  external  configuration,  the 
internal  structure,  the  vital  phenomena  of  health  and  the  functions 
of  each  of  the  different  organs.  Chemistry  and  physics  are  essential 
for  such  a  comprehension,  both  in  their  own  immediate  relations 
and,  too,  in  connection  with  zoology  and  botany  bearing  upon  the 
interpretation  of  disease  causes.  It  is  possible  that  one  without 
this  knowledge,  a  layman,  may  recognize  various  common  morbid 
conditions  (as  wounds,  fractures  of  bones,  catarrhs,  blisters,  etc.), 
may  name  them  correctly,  and  even  treat  them  correctly  on  the  basis 
of  traditional  information  empirically  acquired ;  and  by  frequent  ob- 
servance of  such  conditions  may  accumulate  a  fair  amount  of  skill 
in  their  diagnosis  and  treatment.  This  is  known  as  empirical  knowl- 
edge. But  to  be  able  to  scientifically  interpret  the  complex  picture 
presented  by  disease,  to  understand  the  whole  trend  of  the  process, 
its  signs,  its  inception,  and  its  recovery,  and  moreover  to  practice  a 


6  .  Introduction. 

rational  method  of  treatment,  is  possible  only  to  those  who  have 
become  versed  in  these  basic  branches  of  learning.  Only  unpre- 
judiced observation  of  nature  and  careful  scientific  study  based 
upon  anatomy  and  physiology,  can  give  such  insight.  "To  attempt 
to  guess  by  speculation  what  is  hard  to  learn  even  by  thorough 
investigation  has  failed  in  this  as  in  every  other  field  of  natural 
philosophy."  (Samuel.)  "The  enigmas  of  disease  are  far  too 
complex,  the  intermingling  of  forces  in  the  higher  forms  of  life 
are  far  too  involved,  that  thought  alone  should  successfully  recog- 
nize such  threads,  not  even  to  mention  their  absolute  demonstra- 
tion. The  pages  of  general  pathology  are  filled  with  the  vanity  of 
such  attempts."     (Samuel.) 

Our  knowledge  of  disease  is  primarily  obtained  from  observa- 
tion of  the  external  appearances  of  diseased  human  beings  and  ani- 
mals, from  accumulation  bi  experience  with  the  external  manifesta- 
tions of  disease  (clinical  observation) .  As  long  as  autopsies  were 
not  permitted  upon  the  bodies  of  the  dead,  diseases  received  con- 
sideration only  from  such  external  features ;  and  there  existed  only 
a  symptomatic  classification  of  disease.  It  was  customary  to  speak 
of  jaundice,  dropsy,  ardent  fevers,  nervous  fever,  etc..  as  diseases, 
and  to  endeavor  to  explain  by  clever  theories  and  all  sorts  of  base- 
less ideas  the  origin  of  internal  afifections,  whose  cause  and  location 
were  for  the  most  part  unknown.  They  were  regarded  as  mysteri- 
ous occurrences,  for  which  evil  spirits  or  the  influence  of  the  stars 
on  the  lower  world  should  be  held  responsible ;  and  knowledge  of 
pathology  and  the  art  of  healing  as  well  had  to  be  groped  for  in 
darkness.  Nothing  beyond  those  morbid  conditions  caused  by 
wounds,  by  gross  external  violence,  or  such  affections  of  the  skin  or 
mucous  surfaces  which  were  patent  to  the  eye,  was  dealt  with  in  a 
less  confused  manner. 

In  many  lines  the  physicians  of  antiquity,  who  sought  to  deter- 
mine the  nature  of  disease  by  dissection  of  human  and  animal 
cadavers,  gained  astonishing  experience,  practical  skill  and-  an  ac- 
quaintance with  the  subjects,  as  is  manifest  from  the  clever  experi- 
ments and  methodical  investigations  of  these  early  thinkers.  But 
in  the  centuries  of  the  Middle  Ages,  so  barren  of  medical  advance- 
ment, even  long  after  the  founding  of  the  universities  (which  oc- 
casionally did  succeed  in  making  isolated  discoveries  of  value  in 
connection  with  physiology)  medical  science  became  stationary  and 
fixed,  hemmed  in  betw-een  philosophical  systems  on  the  one  hand 
and  all  manner    of    outgrowths    from    a    purely    speculative    and 


Sources  of  Pathology.  7 

hypothesis-building  science  on  the  other.  The  learned  doctors,  with 
their  schools  of  practically  nothing  more  than  mere  dogma,  who 
had  no  acquaintance  with  the  structure  and  vital  functions  of  the 
body  save  what  could  be  gained  from  its  exterior,  knew  little  more 
than  the  charlatans  of  their  times.  \'eterinary  medicine  was  prac- 
ticed bv  butchers,  farriers  and  grooms,  wdiose  information  and 
practical  knowledge  were  based  upon  the  doctrines,  conceptions 
and  reci]ies  handed  down  from  former  generations. 

At  the  present  time  clinical  observation  is  no  longer  limited  to 
the  mere  detection  of  the  external  signs  of  disease,  but  seeks  an 
explanation  for  them,  searches  for  evidence  of  the  internal  morbid 
processes  and  for  the  precise  location  and  for  the  causes  of  disease, 
calling  to  its  aid  every  means  of  anatomical  and  physiological  in- 
vestigation and  contributing  materially  to  the  complete  develop- 
mental history  of  disease. 

In  point  of  time  the  real  development  of  pathological  science 
corresponds  with  the  period  when  first  the  study  of  the  exact  loca- 
tion of  disease  was  begun  with  the  aid  of  the  dissecting  scalpel  and 
the  microscope.  jMorbid  anatomy  came  to  be  recognized  as  the 
foundation  stone  of  scientific  medicine,  and  remains  the  most  im- 
portant landmark  in  experimental  studies.  It  was  recognized  that 
definite  symptoms  are  related  with  certain  structural  alterations, 
that  it  is  possible  to  make  inferences  as  to  the  altered  state  and 
structure  of  the  organs  from  given  disturbances  of  function,  and 
that  the  symptomatologv  of  a  case  may  thus  furnish  a  basis  for 
the  anatomical  diagnosis  and  the  anatomical  conception  of  the  dis- 
ease in  hand.  IMany  of  the  alterations  of  disease  are  of  such  a 
character  that  the  position,  shape,  consistence,  color,  weight  and 
contents  of  the  parts  affected  are  strikingly  dififerent  from  the 
characteristics  in  health,  and  even  the  unaided  eye  sees  at  once 
whv  svmptoms  must  have  been  induced ;  and  from  the  study  of 
such  evidence  afforded  by  the  dead  bodies  of  diseased  human  beings 
and  animals  there  has  been  accumulated  a  large  amount  of  data  ana 
statistics  toward  the  establishment  of  a  clear  insight  into  the  develop- 
ment, cause  and  termination  of  disease.  Visceral  anatomy  along 
with  visceral  phvsiology  has  taught  us  what  we  know  of  the  prin- 
ciples governing  the  action  of  the  heart,  the  circulation  of  the  blood, 
atmospheric  interchange  in  the  lungs,  the  functions  of  the  digestive 
and  urogenital  tracts,  and  no  little  part  of  the  pathology  of  the 
sensory  organs  ;  and  it  is  quite  possible  for  one  to  draw  conclusions 
from  given  anatomical  changes  how  the  mechanism  of  the  grosser 


8  .       Introduction. 

parts  of  the  body  is  interfered  with,  fails  or  becomes  irregular, 
as  in  case  of  cardiac  obstruction,  obstruction  of  the  blood  vessels 
or  intestinal  canal  by  clots  of  blood  or  foreign  bodies,  or  how  in- 
testinal displacement  or  unusual  taxing  of  the  organs  must  or 
may  lead  to  disturbances.  The  entire  group  of  physiological 
methods  of  investigation  are  of  value  in  the  solution  of  pathological 
problems ;  physics  and  chemistry  aid  in  explanation  and  find  the 
most  varied  application  in  their  study.  There  has  been  developed 
in  pathology  along  the  lines  of  its  special  studies  a  series  of  prac- 
tical methods  of  animal  experimentation,  known  as  Experimental 
Pathology,  affording  accurate  information  in  many  of  the  problems 
of  pathogenesis  and  supplying  valuable  demonstrations  of  the  cor- 
rectness of  our  best  established  observations  and  conclusions.  One 
may  at  will,  by  operative  procedure  upon  living  animals,  by  ligation 
or  occlusion  of  blood  vessels  or  ducts  of  glands,  produce  and  imitate 
mechanical  changes  of  various  types ;  and  it  is  quite  possible  by 
killing  the  experiment  animal  at  any  time  to  note  precisely  the 
anatomical  changes  and  progress  of  the  disease  thus  induced,  from 
which  the  course  of  actual  diseases  of  a  corresponding  type  have 
come  to  be  well  appreciated.  By  operative  removal  of  some  organ 
or  part  of  an  organ,  it  is  possible  to  obtain  an  idea  as  to  the  results 
which  are  likely  to  follow  analogous  disease  processes  in  the  same 
part,  as  in  case  of  the  thyroid  gland,  liver,  kidney  or  adrenal.  All 
our  knowledge  of  regenerative  growth  of  tissues,  the  healing  of 
wounds,  the  union  of  fractured  bodies  and  of  the  general  process  of 
inflammation  we  owe  directly  to  experimental  studies  on  animals. 
By  administering  to  animals  various  types  of  material  of  ap- 
parently poisonous  character,  it  has  been  possible  to  study  the  action 
of  a  wide  range  of  substances  and  to  acquire  the  essential  basis 
for  diagnosis  of  the  intoxications.  The  complete  life  history  of  the 
animal  parasites,  their  development  and  multiplication  in  the  human 
and  animal  body,  and  the  diseases  caused  by  them,  have  been  worked 
out  by  means  of  animal  experimentation  in  a  really  classical  man- 
ner; and  the  practical  application  of  this  knowledge  in  food  exami- 
nation, in  meat  inspection  and  in  other  lines  of  prophylaxis  against 
disease,  are  exceedingly  numerous  and  have  led  to  marked  diminu- 
tion of  such  diseases  as  hydatids,  trichinosis  and  mange.  But  above 
all  else  animal  experimentation  has  lifted  the  dark  cloud  which 
formerly  obscured  the  nature  of  infectious  diseases;  and  only  from 
successful  attempts  in  transmission  by  inoculation  has  it  been  pos- 
sible to  explain  and  obtain  precise  knowledge  as  to  the  real  nature 


Importance  of  Pathology.  g 

of  plagues  and  their  development.  As  long  as  these  methods  were 
not' employed  superstition  and  fear  dominated  mankind  whenever  a 
pestilence  appeared.  To-day,  with  realization  of  the  conditions 
essential  for  infection  and  the  modes  of  transmission,  medical 
acumen  has  determined  the  surest  preventive  measures  for  con- 
trolling and  combatting  these  diseases ;  and  even  the  worst  epi- 
demics, as  of  plague  and  cholera,  have  largely  lost  their  terrors. 
With  confidence  the  work  of  extirpation  is  being  carried  forward, 
and  medical  science,  crowned  with  success,  has  completely  stamped 
out  a  number  of  these  infections  and  is  daily  solving  the  difficulties 
in  the  prevention  and  cure  of  such  evils. 

To  sympathetic  persons  it  may  indeed  seem  a  serious  thing  that 
we  be  forced  for  our  own  advantage  to  make  use  of  the  sufferings 
of  lower  animals  in  order  to  avert  such  dangers  from  ourselves 
and  to  purchase  by  animal  sacrifice  the  means  of  combatting  con- 
tagion. But  the  instinct  of  self-preservation  impels  man,  just  as 
the  necessity  for  food  with  any  animal  demands  the  death  of  other 
creatures.  The  slaughter  of  animals  for  sport  is  far  worse,  and 
productive  of  more  pain  to  them ;  and  many  of  the  methods  of  kill- 
ing in  the  kitchen  of  the  epicure  are  much  less  excusable  than  any 
of  the  practices  in  the  whole  range  of  deplored  animal  inoculation, 
so  unavoidable  for  the  establishment  of  medical  science.  When  it 
is  realized  that  without  the  results  obtainable  by  such  work — Ex- 
perimental Pathology — millions  of  people  must  forever  be  threatened 
by  early  death  from  pestilence,  as  of  old,  when  countless  numbers 
were  sufferers  in  these  epidemics  and  were  hurried  off  before  their 
time  and  when  destructive  cattle  plagues  forced  heavy  burdens 
on  the  land,  whole  hecatombs  of  animals  for  which  the  experi- 
mentalist must  account  must  appear  but  a  trifling  matter.  Prohi- 
bition of  animal  experimentation,  as  is  sought  by  unrestrained 
zoomania,  would  be  equivalent  to  prohibiting  the  cure  of  the  sick; 
since  nature  affords  for  many  affections  no  means  for  restoration 
other  than  the  blood  of.  inoculated  animals.  Human  education  and 
the  high  ethical  tone  of  medical  science  will  certainly  be  sufficient 
security  that  experimental  pathology  in  pursuit  of  its  purposes  will 
not   lend   itself  to   useless   animal  torment. 


HISTORY  OF   PATHOLOGY 

Much  of  our  experience  and  knowledge  of  the  diseases  of  man 
and  of  the  lower  animals  has  come  down  to  us  from  antiquity.  The 
gift  of  observation  and  the  faculty  of  reasoning,  as  well  as  his 
desire  to  restore  impaired  health,  impelled  primitive  man  to  formu- 
late some  kind  of  ideas  regarding  the  origin  and  nature  of  disease. 
And  as  the  grade  of  individual  and  popular  intelligence  advanced 
and  as  experience  grew  in  value  with  its  transmission  from  genera- 
tion to  generation  by  traditions  and  records,  so  our  conceptions  of 
disease  expanded  and  our  knowledge  advanced,  or  on  the  other  hand 
mistaken  ideas  took  deeper  hold  or  false  notions  once  discarded  again 
came  into  prominence.  History  informs  us  that  for  some  thousands 
of  years  there  had  been  attained  considerable  skill  in  the  art  of 
healing  among  the  Babylonians,  Persians.  Egyptians,  Hindoos, 
Israelites,  Greeks  and  Romans  both  among  the  priests  and  in  the 
hands  of  a  special  class  of  physicians ;  and  although  religion  and 
superstition,  mysticism  and  philosophical  speculation  had  much  in- 
fluence over  it,  medicine  really  w^as  possessed  of  a  very  notable  fund 
of  information. 

In  the  fourth  and  fifth  centuries  before  Christ  considerable  work 
was  done  by  physicians  and  naturalists  like  Alkmseon  (B.  C.  54o). 
Hippocrates  IT,  the  son  of  Heraclides  (B.  C.  460-375  )  and  Aristotle 
(B.  C.  384-323)  in  the  line  of  dissection  of  animals  for  inference 
to  the  supposedlv  similar  structure  of  the  human  body,  human 
cadavers  being  but  rarely  obtained  for  purposes  of  dissection.  Dis- 
semination of  the  knowledge  of  medicine  -which  existed  was  ad- 
vanced by  the  great  schools  of  learning,  like  the  Museum  and 
Serapeum  in  Alexandria  with  their  magnificent  libraries  (700,000 
rolls  of  papyrus  in  the  Museum  and  300,000  in  the  Serapeum),  and 
by  the  profuse  literature  of  the  Greeks  and  Romans.  To  some 
extent,  doubtless,  veterinary  medicine  shared  in  this;  being  practised 
both  by  the  general  physicians  and  by  a  special  class  of  veterinarians, 
known  as  inulonicdici,  hippiatrcs  (I'TTTros,  horse:  larpoi,  physician), 
kteiiiatres  (kt>}vos,  domestic  ammsLl ;  iarpdi,  physician)   and  vcterinarii; 


Early  History.  ii 

yet  in  a  large  measure  it  remained  in     its   primitive   condition   in 
the   hands    of   shepherds   and    farmers. 

At  the  beginning  of  our  present  era  medicine  was  chiefly  domi- 
nated by  the  teachings   formulated   by   Hippocrates  and  Aristotle 
in    their    general    writings.      The    study    of    comparative    natural 
science,     instituted    by     Aristotle,     laid     the     foundation     of     our 
knowledge  of  animal  biology,  of  comparative  anatomy  and  physi- 
ology;    while   Hippocrates    and    after    him   the    physicians    of   his 
school  established  pathology.     At  that  time  it  was  held  that  there 
were  in  the  animal  and  hmuan  bod)'  four  cardinal  humors,  "blood, 
mucus,  and  yellow  and  black  bile."     It  was  taught  that  a  proper 
relationship  between   these    (crasis)    insured   health;   and   that   dis- 
ease depended   upon  the  occurrence  of  lack  or  excess  of  one  or 
other,  that  is  upon   some   modification   of  their   relationship    (dys- 
crasis).     Next  to  the  blood,  the  principal  vital  humor,  Hippocra- 
tes placed  mucus  in  order  of  importance,  because  it  is  often  dis- 
charged  in    large    quantities    from   the   nose   and   was   thought   to 
come  from  the  brain  and  to  escape  through  the  ethmoidal  open- 
ings.    Yellow  bile   was   often   seen   in   vomit :  but  black  bile  was 
entirelv  a  product  of  the  imagination  and  was  supposed  to  arise 
in   the    spleen.      The   basis   of   vital   phenomena    was    supposed   to 
be    the    inspired    air    {pnciuna,    the    breath    of    life),    which    was 
thought  to  contribute  warmth  to  the  body.     In  conformity  with 
the    accepted    theory    of    corruption    of    the    humors,    therapeutic 
measures  were  directed  to  a  riddance  from  the  system  of  the  ma- 
terial   which    had    caused    the    "dyscrasia ;"    and    for    this    reason 
evacuants,    diaphoretics,   diuretics   and   venesection   played   an   mi- 
portant  part   in   those   times.     The  importance   which   Hippocrates 
ascribed  to  these  fluids  or  humors  led  to  the  application  by  later 
generations    of    the    name    Humoral    Pathology    to    this    system. 
The  solid   structures   of  the   body   were   not   entirely   disregarded, 
but    only    vague    ideas    prevailed    in    relation    to    them.      There 
was   a   theory    (Democrites)    that  the   solid   parts  were   made   up 
of   particles   known    as    c.toms,    between    which   there    were   pores 
[for  the  passage  of  air  and  humors],  that     the     width     of     these 
pores    varied    with    the    varying    density    of    deposition    of    the 
atoms,  and  that  by  some  such  method  the  state  of  the  body  was 
regulated.     To  this  extent,  therefore,  there  was  a  Solid  Pathology, 
which,     however,     found     but     few     adherents.       Efforts    toward 
such   theoretical    explanations    found    support    particularly    in    the 
schools  of  philosophy ;  and  tenacity  of  such  views  and  the   rigid 


12  History  of  Pathology. 

adherence  to  authority,  together  with  constant  seeking  after  the 
keenest  dialectic  in  argument,  gave  to  one  school  of  physicians 
of  the  day  the  character  of  "dogmatists ;"  while  others  discarded 
entirely  speculative  reasoning  and  called  themselves  "empiricists," 
boasting  that  their  methods  of  practice  were  based  entirely  on 
experience.  They  rejected  the  study  of  anatomy  as  superfluous  ; 
in  which,  however,  the  dogmatists,  although  essentially  bookmen 
and  theorists,  made  some  progress. 

In  the  middle  of  the  second  century  Claudius  Galenus  (born  in 
Pergamon,  Asia  Minor,  A.  D.  131  ;  educated  in  Smyrna,  Corinth 
and  Alexandria,  and  afterwards  practicing  his  profession  in  Rome  ; 
died  A.  D.  206),  noted  both  for  his  discoveries  and  as  a  prac- 
titioner, revolutionized  medical  science  by  his  efforts  to  harmonize 
the  prevailing  theories  with  practical  experience  and  thus  give 
them  a  real  value,  and  by  his  work  in  the  establishment  of  ra- 
tional scientific  methods  through  comparative  anatomy  and  ex- 
periments upon  living  animals.  Throughout  the  middle  ages,  even 
into  the  fifteenth  century,  the  theories  of  Galen,  whose  discoveries 
were  numerous  and  whose  extensive  writings  contain  much  that 
is  of  descriptive  value,  were  held  in  esteem  and  respect,  par- 
ticularly his  opinions  upon  anatomy  and  physiology. 

Through  studies  of  this  character  at  the  hands  of  physicians 
a  close  relationship  developed  between  veterinary  medicine  and 
human  medicine ;  but  there  were  other  influences  which  aided  in 
the  development  of  comparative  pathology.  Agriculturists,  like 
Xenophon,  Cato,  Columella,  and  Virgil,  and  veterinary  specialists 
who  in  Rdman  times  attained  an  independent  standing,  and 
among  whom  should  be  mentioned  Apsyrtos  (circa  290-350, 
A.  D.)  and  Publius  Vegetius  Renatus  (circa  540,  A.  D.)  as  es- 
pecially distinguished,  there  were  collected  and  recorded  in  litera- 
ture their  experiences  with  various  diseases,  especially  epidemic 
affections  among  animals.  Although  there  is  much  useless  em- 
piricism included  in  the  dissertations  of  these  writers,  there  are 
also  no  little  excellence  of  observation  and  soundness  of  thought ; 
and  the  works  of  the  last-named  author,  like  those  of  Galen, 
served  for  centuries  as  valuable  spurces  of  information. 

The  general  collapse  of  the  sciences  after  the  fall  of  the 
Roman  Empire,  during  the  time  of  migration  of  the  European 
peoples  and  the  period  of  the  Middle  Ages,  resulted  in  a  long 
stagnation  in  medicine.  Practically  all  that  is  worth  considering 
was  the  preservation  of  the  writings  of  the  ancients,  for  which  we 


Middle  Ages  and  Modern  History.  13 

are  chiefly  indebted  to  the  monks,  working  as  copyists  in  the 
monasteries.  Technical  medical  skill  made  scarcely  any  note- 
worthy progress.  With  the  founding  of  the  universities  in  the 
thirteenth  to  fifteenth  centuries,  when  a  resumption  of  anatomical 
investigations  gradually  became  possible,  and  with  the  discovery 
of  the  printing  art,  which  stimulated  the  translation  and  wide 
'dissemination  of  the  works  of  Grecian  and  Roman  authors,  there 
began  a  new  epoch.  The  luminous  works  of  the  human  anato- 
mists like  Vesalius,  FaJlopius  and  Eustachius,  the  experimental 
researches  of  Serv^etus  and  Columbus  Cesalpinus.  and  particularly 
William  Harvey's  (1578-1658)  discovery  of  the  true  conception 
of  the  circulation  of  the  blood,  led  directly  to  the  recognition  of 
the  errors  in  Galen's  system  and  to  a  reorganization  of  medical 
science.*  As  usual  pathology  again  fell  into  errojr,  ascribing,  un- 
der the  influence  of  prevailing  views  in  natural  science,  the 
various  processes  of  disease  and  their  causation  now  to  this,  ndw 
to  that  physical  or  chemical  factor.  Speculative  hypotheses  took 
precedence  of  actual  experiment,  and  attempts  at  proper  explana- 
tion were  quite  lost  in  the  fancies  of  the  individuals.  Some  were 
followers  of  the  "chemical  school"  founded  by  Sylvius,  and  en- 
deavored to  explain  every  fault  by  chemical  changes  in  the  com- 
position of  the  bod\-,  as  the  introduction  of  "sharps"  (Boer- 
haave)  ;  others,  the  "neuropathologists,"  when  the  importance  of 
the  nervous  system  became  .recognized,  laid  stress  upon  the  in- 
fluence of  the  nerves  (William  Cullen),  or  upon  the  eflrect  of 
"stimuli"  and  the  irritability  of  the  tissues  (the  theory  of  ex- 
citability of  Haller  and  Erown).  Others,  basing  their  views  upon 
mechanics,  believed  the  vital  phenomena  of  morbid  disturbances 
depended  upon  mechanical  faults  of  relationship  ("mechanical 
school,"  founded  by  Santoro,  1 561-1635,  Borelli,  1608-1677). 
Still  others  spoke  of  "vital  spirits"  circulating  in  the  body,  of 
"forces,"  of  the  power  of  the  "entities"  (Paracelsusf).  or  made 
some  injury  to  the  immortal  soul  the  real  principle  of  disease 
(G.  E.  Stahl.  1660-1734).  These  doctrines  were  denominated  wVa/- 
ism  and  airiiiiism.  Such  ideas  have  found  adherents  even  as  late 
as  within  the  nineteenth  century,  clothed  usually  in  high-sounding 
foreign  verbiage  to  make  the  greater  impression. 

Along  with  these  speculative  theories,  however,  exact  clinical 


•Compare  Eichbaum,    GachicMe  df  HcilJ;undc:   Berlin.    Pareys'    Verl..    1SS5. 

tTheophrastus  Bombastus,  whose  proper  name  was  Paracelsus,  distinguished 
different  forces,  an  ens  astrale  (power  of  the  stars),  an  ens  naturale,  spirituale, 
venerd,  etc.,  as  factors  in  life  and  disease. 


14  History  of  Pathology. 

observation,  physiological  experimentation  and  anatomical  dissec- 
tion grew  more  and  more  toward  a  plane  of  real  excellence,  af- 
fording an  increasing  clearness  of  insight  into  the  processes  which 
obtain  in  both  healthy  and  diseased  bodies.  The  anatomical 
changes  shown  in  necropsies  directed  attention  to  the  topography 
of  disease.  Morgagni  (1682-1771).  a  teacher  of  anatomy  in 
Padua,  in  his  work,  "Dc  Scdibus  ct  Causis  Morbontin"  (1761), 
outlined  the  first  comprehensive  and  system.itic  exposition  in  this 
direction  and  came  to  be  regarded  as  the  founder  of  pathological 
anatomy.  From  efforts  to  correlate  manifestations  of  disease  of 
the  various  organs  with  the  presence  of  anatomical  changes,  arose 
the  school  of  Pathological-anatomical  Diagnosis,  to  which  is  due 
the  discovery  of  a  number  of  valuable  methods  of  diagnosis  (per- 
cussion, thermometry,  the  microscope,  chemical  analysis),  and 
which  had  as  its  founders  men  like  Bichat,  Pinel,  Corvisart, 
Dupuytren,  Auenbriigger,   Laennec  and  Rokitansky. 

The  advances  in  physiology  inaugurated  bv  Johannes  Miiller 
(1801-1858)  and  the  cellular  theory  formulated  by  Th.  Schwann, 
along  with  the  development  of  microscopic  anatomy,  are  respon- 
sible for  an  important  change  from  the  older  conceptions  of  dis- 
ease, giving  us  as  a  basis  for  our  ideas  of  morbid  processes  a 
cellular  pathology,  first  proposed  by  Rudolph  Virchow  (1858), 
who  referred  the  real  seat  of  disease  to  the  individual  cells  and 
the  tissues,  and  regarded  disease  as  depending  upon  the  reaction 
of  these  to  harmful  influences.  Although  it  is  but  about  fifty 
years  ago  that  Schonlein's  school  looked  on  disease  as  some  sort 
of  living  thing  of  extra-corporeal  origin,  entering  the  bodies  of 
men  and  animals  like  a  parasite  and  expelled  by  our  therapeutic 
measures  ;  yet  in  the  interim  the  study  of  Aitiology  has  developed 
the  definite  view  that  disease  is  but  the  manifestation  of  mor- 
phological, chemical  and  functional  changes  which  are  induced  by 
the  most  varied  harmful  influences  upon  the  cells  and  tissues, 
chemical  or  physical ;  and  thus  to-day,  through  uniform  and  ex- 
act methods  of  objective  research,  clear  conceptions  and  positive 
knowledge  are  in  hand  relative  to  most  diseases. 

As  far  as  comparative  pathology  is  concerned,  it  too  was  com- 
pletely dormant  from  the  fourth  until  the  eighteenth  century,  at 
first  because  of  the  general  depression  in  science,  later  because 
medical  practitioners  had  but  little  interest  in  the  diseases  of  ani- 
mals when  human  medicine  was  developing  along  these  newer 
lines,  but  especially  because  of  the  aversion  which  men   came  to 


Comparative  Pathology.  15 

hold  for  even  mere  contact  with  the  dead  bodies  of  animals. 
Among  the  rare  publications  appearing  in  the  middle  ages  there 
is  onlv  one  large  work  on  the  anatomy  of  the  horse  (issued  in 
1598  by  the  \'enetian  senator,  Carlo  Ruini,  but  probably  the 
product  of  some  physician)  which  is  at  all  worthy  of  note  as 
showing  any  advance  in  knowledge.  At  the  same  time  the  nat- 
ural history  of  the  domestic  animals  was  considerably  advanced 
by  C.  Gessner  (15 16-1565)  and  Aldrovandi  (1522- 1605).  Prac- 
tice of  veterinary  medicine  w^as  relegated  more  and  more  to  far- 
riers, executioners  and  butchers  and  naturally  drifted  into  the 
crudest  sort  of  empiricism.  However,  when  skill  in  riding  and 
horses  became  more  prized  in  the  courts  of  princes  and  in  war, 
there  was  a  change  for  the  better;  and  Italian,  French  and  Ger- 
man masters  of  the  stable  (Pignatelli,  J\Iarx  Fugger,  Bohme, 
Winter  von  Adlersfliigel,  Robertson,  J.  von  Sind,  Solleysel,  Pluvi- 
nel.  Lafosse)  published  a  number  of  works  upon  the  diseases  of 
the  horse.  From  the  eighteenth  century  physicians  once  more  be- 
gan to  frequently  pay  attention  to  animal  pathology;  the  necessi- 
ties arising  from  devastating  epidemics  among  cattle,  particularly 
cattle  plague,  stimulating  the  members  of  the  medical  faculties 
to  endeavor  to  stamp  out  these  diseases  and  to  publish  numerous 
articles  upon  investigations  bearing  in  this  direction  (Ramazzini, 
Lancisi,  Schroeck,  Golike,  Kamper,  Sauvages,  von  Haller,  Paulet). 
In  the  years  from  1762- 1790,  in  most  of  the  [European] 
states,  schools  of  veterinary  medicine  were  established,  the  first 
being  inaugurated  by  Bourgelat  in  Lyons  and  Alfort.  With  this 
step  comparative  medicine  found  a  place  in  scientific  institutions, 
later,  after  various  changes  in  organization,  assuming  the  rank  of 
independent  colleges  or  becoming  incorporated  with  the  universi- 
ties. 

The  first  teachers  of  veterinary  medicine  were  for  the  most 
part  physicians ;  and  even  to  the  present  the  progress  of  the  sci- 
ence is  in  close  sympathy  and  relation  with  human  medicine. 
However,  the  men  who  in  the  nineteenth  century  have  been  edu- 
cated to  the  dignity  of  independent  investigators  and  to  a  new 
standard  as  veterinarians,  have  broadened  comparative  medicine 
to  a  manv  sided  field ;  and  the  results  of  their  discoveries  and 
their  practical  achievements  have  become  of  importance  not  only  to 
the  farming  and  cattle-raising  industries,  but  to  the  general  wel- 
fare of  mankind  as  well  when  one  takes  into  consideration  the 
consumption  of  meat  and  the  dangers  of  animal  epidemics. 


PREDISPOSITION   TOWARD    DISEASE 

Any  living  being  becomes  affected  by  disease  when  no  longer 
able  to  adapt  itself  to  its  environment  and  to  the  demands  to 
which  the  functional  ability  of  its  cells  and  organs  is  subjected. 
As  soon  as  such  external  influences  exceed  the  limits  of  endur- 
ance, as  soon  as  they  so  affect  the  cells  and  organs  as  to  induce 
alteration  of  function,  they  become  causes  of  disease.  There  is 
really  nothing  upon  which  the  animal  body  is  dependent  or  with 
which  it  is  related,  but  may  on  occasion  cause  the  onset  of 
disease — nutrimient,  air,  light,  temperature,  the  various  animal 
and  vegetable  organisms  about  it.  the  varied  accidents  of  nature, 
its  own  active  and  passive  relations,  as  well  as  every  physiological 
process  going  on  in  its  economy ;  and  the  very  same  factors, 
which  are  generally  essential  for  the  maintenance  of  existence 
and  the  well-being  of  the  individual,  may  become  agencies  of 
harm  and  noxious  {nocere,  to  harm)  influences  productive  of 
disease. 

Whether  the  individual  should  experience  the  harmful  possi- 
bilities of  such  factors  or  not  depends  upon  the  inherited  po- 
tentiality of  the  organism,  the  functional  capabilities  of  its  cells 
and  tissues,  and  upon  the  efificiency  of  its  protective  and  reg- 
ulative mechanism.  Sensitiveness  to  noxious  influences,  known 
as  Predisposition,  and  insensitiveness  or  insusceptibility,  commonly 
spoken  of  under  the  terms  Resistance  or  Immunity,  are  by  nature 
widely  different  among  different  species  and  individuals  and  even 
among  the  different  tissues  in  the  same  animal ;  and  are  subject  to 
considerable  variations  and  abnormalities.  The  polar  bear,  the 
Esquimau  dog  and  the  reindeer  are  accustomed  to  the  cold  of  the 
north,  but  sicken  in  the  temperature  of  warmer  climes ;  many  ani- 
mals thoroughly  adapted  to  the  tropics,  perish  when  transferred  to 
cooler  regions  even  though  furnished  with  their  usual  food.  Indi- 
vidual animals  of  the  same  species  often  manifest  differences  of 
susceptibility,  as  where  in  herds  of  cattle  or  even,  as  is  often  ob- 
served, in  a  number  of  cattle  kept  in  the  same  stable,  some  path- 


Variations  in  Predisposition.  17 

ogenic  influence  equally  operative  upon  the  whole  group  fails 
to  pcoduce  its  effect  upon  all,  certain  individuals  resisting  it  suc- 
cessfully;  or  it  is  often  noticed  that  here  and  there  an  animal 
sickens  under  conditions  quite  favorable  for  most  of  its  species. 
The  difference  between  different  tissues  in  predisposition  and  im- 
munity may  be  seen  in  comparing  the  skin  and  mucous  mem- 
branes. The  surface  of  the  skin,  with  its  hard  epithelial  cover- 
ing, is  much  less  sensitive  to  irritative  substances  than  are  the 
delicate  mucous  membranes ;  the  mucous  membrane  of  the  stom- 
ach in  the  living  animal  is  resistant  to  the  action  of  acids,  but 
that  of  the  lower  end  of  the  intestinal  tract  may  be  injured  by 
the  acid  of  the  gastric  juice. 

A  number  of  poisons  (snake  venom,  tetanus  toxine)  are  en- 
tirely harmless  when  taken  into  the  alimentary  canal ;  although,  if 
introduced  by  way  of  lesions  of  the  skin  into  the  tissues,  they 
are  extremely  pathogenic. 

Especial  interest  attaches  to  the  differences  in  predisposition 
and  immunity  toward  the  viruses  of  infectious  diseases.  In  all 
infectious  diseases  we  have  to  deal  with  poisonous  materials 
caused  by  micro-organisms.  These  micro-organisms  (micro- 
phytes, vegetable  microscopic  organisms ;  fnicro.coa,  animal  micro- 
scopic organisms)  gain  entrance  to  the  body  by  alimentation,  or 
by  the  respiratory  path,  or  through  ivounds,  or  may  even  actively 
penetrate  the  tissues  should  they  be  in  close  relation  with  the 
skin  or  mucous  surfaces.  Within  the  body  structure  they  mul- 
tiply for  a  time  and  work  harm  to  the  tissues  chiefly  by  the 
specific  poisons  existing  in  their  protoplasm  (that  is,  in  the  bodies 
of  the  microbes)  or  by  poisons  elaborated  by  them,  diffused  in 
the  tissues  and  taken  up  by  the  blood.  In  the  contest  waged 
with  these  microscopic  foreign  invaders  a  twofold  task  is  set  for 
the  animal  body ;  it  must  in  the  first  place  destroy  the  microbes 
and  at  the  same  time  must  render  their  toxines  inert.  One  ani- 
mal may  accomplish  this  with  ease  ;  another  with  difliiculty.  Some 
species  of  animals  are  by  nature  uninfluenced  by  the  toxine  of  an 
infection  which  is  sure  to  produce  disease  in  another  species ; 
thus  cattle  are  immune  to  glanders,  the  horse  to  pulmonary 
tuberculosis,  and  chickens  bear  large  doses  of  tetanus  toxine  with- 
out injury  to  health. 

Such  absence  of  reaction  to  infections  and  their  toxines  in  an 
animal  species  is  spoken  of  as  natural  immunity.  It  is  to  be 
explained  from  one  standpoint  by  the  idea  that  the  cells  and  tis- 


i8  Predisposition  and  Immunity. 

sues  of  the  immune  animal  have  no  affinity^  or  but  little  affinity 
(chemical  affinity),  toivard  the  toxines  of  the  infection.  The 
poisonous  elements  simply  do  not  enter  into  combination  with 
them.  For  example,  the  nervous  system  of  the  turtle  is  absolutely 
immune  to  the  toxines  of  diphtheria  and  tetanus,  and  these  sub- 
stances may  be  injected  into  the  animal  entirely  without  effect. 
Yet  the  toxines  thus  introduced  may  remain  in  the  bodies  of  the 
experiment  animals  for  months  without  being  rendered  inert  by 
the  juices  ;  and  should  the  blood  of  such  a  turtle  be  injected  into 
some  susceptible  animal  it  will  act  in  the  sarne  manner  upon  the 
latter  as   would   the   toxine   itself, 

FYom  a  second  point  of  view  it  is  to  be  recognized  that  im- 
munity may  depend  upon  the  fact  that  some  of  the  cells  of  the 
animal  in  question  are  able  to  take  up  and  digest  micro-organisms, 
and  thus  render  them  harmless  (Phagocytosis).  This  power  of 
seizing  and  ingesting  small  particles,  organic  and  inorganic,  or 
dead  and  living  cells,  is  peculiar  especially  to  the  motile  types  of 
leucocytes  (wandering  cells,  white  blood  cells),  but  is  also 
possessed  by  giant  cells,  splenic  and  medullary  cells,  and  even 
fixed  connective  tissue  cells  (as  endothelium)  ;  and  plays  an 
important  part  in  the  economy  of  the  body.  Its  significance  has 
been  pointefl  out  especially  by  the  ingenious  investigations  of 
Metschnikoff,  Leber, and  Bordet.  These  phagocytes  act  as  scaven- 
gers, taking  up  and  making  awa}'  sometimes  with  blood  debris, 
nuclear  fragments,  pigment,  fat  globules  and  all  sorts  of  minute 
foreign  particles  with  which  they  come  in  contact.  The  ingestion 
of  such  corpuscular  elements  is  with  them  a  simple  process  of 
feeding.  The  movement  and  approach  of  the  phagocytes  may 
be  induced  bv  a  number  of  stimuli,  as  warmth  or  an  acid,  acting 
upon  their  own  tactile  or  chemical  sensitiveness.  Tn  coming  in 
contact  with  foreign  particles  they  attempt  to  increase  their 
surface  of  contact  as  much  as  possible  [applying  their  protoplasm 
more  and  more  about  the  surface  of  the  particle,  and  thus 
eventually  enveloping  it  in  their  own  material]  ;  and  are  at- 
tracted by  various  chemical  substances  (cheniota.vis) .  [It  is 
but  fair  to  add  here  that  while  the  theory  of  chemotaxis,  as  a 
part  of  the  general  theory  of  "tropisms"  or  of  blind  automaton- 
like response  of  living  things  to  external  forces  or  attractions, 
finds  wide  adherence  among  medical  men  and  biologists,  there 
are  nevertheless  others  who  do  not  accept  such  a  view,  the  latter 
finding  reason  to  believe  that  the  manifestations  which  the  former 


Protective  Substances.  19 

school  attribute  solely  to  non-intelligent  attraction  from  without 
are  really  due  to  an  inherent  power  of  a  low  intelligent  char- 
acter of  the  organisms  showing  them.  These  latter  would 
attribute   even   to   individual   cells   as   the    phagocytes,   a   low   but  1^ 

actual  volitional  power  to  either  originate  or  refrain  from  efiforts 
to  approach  the  foreign  particles  referred  to.]  The  proto- 
plasm of  the  phagocytes  apparently  can  secrete  digestive  juices 
[there  is  reason  to  think  that  certain  granules  seen  in  leucocytes 
are  of  the  nature  of  ferments],  through  the  action  of  which 
they  are  able  to  assimilate  nutritive  matter  and  dissolve  foreign 
bodies. 

In  this  latter  manner,  in  part  at  least,  it  is  possible  that  the 
virus  of  infectious  diseases  may  be  removed  from  the  tissues. 
Nuttall  first  pointed  out  that  in  the  blood  plasma  of  healthy  ani- 
mals there  exist  certain  substances  which  are  capable  of  dissolv- 
ing the  body  matter  of  bacteria,  and  of  thus  destroying  them. 
These  substances,  called  alexins  by  Buchner,  and  complements  by 
Ehrlich  (by  others  addimoifs  and  cyfoscs),  are  products  of  the 
cells,  which  are  either  given  off  by  the  living  cells  (Buchner)  or 
are  set  free  by  cellular  destruction  (Metschnikofif)  ;  and  are 
found  in  varying  amount  in  the  circulating  blood  of  the  indi- 
vidual animals.  An  excellent  example  of  these  substances  is  seen 
in  the  efifect,  discovered  by  Behring,  of  the  serum  of  white  rats 
upon  the  anthrax  bacillus.  If  hundreds  of  thousands  of  anthrax 
germs  are  placed  in  some  serum  from  a  white  rat  (at  37°  C.) 
it  will  be  noticed  after  ten  or  fifteen  minutes  that  the  bacilli 
have  become  swollen  and  degenerated  (granular),  and  after 
from  four  to  seven  hours  that  they  have  completel}'  dis- 
appeared. Canine  or  ovine  serum  does  not  possess  this  power, 
but  should  a  few  drops  of  rats'  serum  be  added  to  sheep,  serum 
the  bactericidal  action  will  immediately  appear.  The  serum  of 
the  horse  also  has  a  strong  bactericidal  power.  It  must  be  clear 
that  the  cause  of  natural  immunity  cannot  be  attributed  to  the 
bactericidal  action  of  the  serum  alone,  for  both  rats  and  horses 
are  susceptible  to  anthrax ;  it  must  be  thought  of,  as  already  men- 
tioned, as  dependent  in  part  upon  the  lack  of  affinity  of  the  living 
cells  for  the  toxines  of  the  infection,  and  in  part  upon  their 
phagocytic   power. 

Just  as  among  different  animal  species  and  individuals  there  may  be 
some  one  kind  which  is  more  highly  resistant  to  poisons  than  the  rest, 
so  there  may  be  met  others   exhibiting  an   excessive    susceptibility  to   such 


20  Predisposition  and  Immunity. 

influences.  For  example,  cats  are  extremely  sensitive  to  carbolic  acid. 
It  is  well  known  that  some  persons  possess  so  marked  a  susceptibility  tc 
a  number  of  substances  and  foods  (as  strawberries,  mushrooms,  crabs, 
lobsters,  cocoa  or  alcohol)  that  after  partaking  of  them  they  experience 
severe  pain,  vomiting  and  cutaneous  eruptions,  and  in  the  same  way  are 
apt  to  be  severely  affected  by  certain  medicaments  (chloroform  or  mor- 
phine) ;  they  are  influenced  by  such  substances,  as  it  were  by  poisons. 
Such  extreme  susceptibility  is  known  as  idiosyncrasy  (i'Sios,  •peculiar; 
i]  ffvyKpd(ns,    combination). 

As  a  rule,  the  predisposition  or  inimiiinty  of  individuals  is 
only  a  relative  one ;  that  is,  it  is  variable  and  of  moderate  degree, 
may  be  increased  or  decreased,  and  is  often  only  temporary. 
Racial  or  specific  immunity  may  also  be  but  relative.  Rabbits 
are  ordinarily  immune  to  symptomatic  anthrax,  but  now  and 
?gain  a  rabbit  is  found  to  be  susceptible  to  this  disease  upon 
inoculation.  Goats,  horses  and  cattle  are  strongly  resistant  to 
swine-erysipelas,  but  if  large  amounts  of  the  virus  are  injected 
intravenously  they  may  show  severe  symptoms.  Young  dogs  are 
somewhat  susceptible  to  anthrax ;  older  dogs  less  so.  Young 
sucking  calves  are  very  rarely  afifected  by  "black  leg"  and  usually 
resist  inoculation  tolerably  well ;  but  as  soon  as  they  begin  to 
eat  vegetable  food  they  become  very  susceptible  to  the  disease 
in  question.  Thus  age  and  food  are  seen  to  have  an  influence 
upon  predisposition  and  immunity.  How  intimately  connected 
'the  latter  factor  is  may  be  inferred  from  the  experiment,  origi- 
nally performed  by  Feser  and  afterward  confirmed  by  others,  in 
which  rats,  if  fed  upon  meat  alone,  are  found  as  a  rule  to  be 
immune  to  anthrax,  while  if  fed  on  bread  they  soon  succumb  to 
inoculation  with  the  virus. 

By  experimentation  it  has  been  shown,  moreover,  that  hunger 
is  a  predisposing  cause,  that  bodily  overexertion  (overheated  ani- 
mals), nutrition  of  restricted  quality  and  excessive  amount  (  as  a 
diet  too  rich  in  fat)  may  have  such  depre'ssing  influence  that 
animals  subjected  to  them'  readily  succumb  to  injurious  agencies 
which  they  would  otherwise  bear,  and  particularly  become  less 
resistant  to  infections.  It  is  also  true  that  certain,  altered  condi- 
tions of  the  tissues  afford  especially  vulnerable  points  for  the 
attack  of  pathogenic  influences ;  for  example,  gastric  catarrhs,  by 
diminishing  the  production  of  hydrochloric  acid,  favor  the 
deposition  and  pathogenic  action  of  bacteria  which  are  otherwise 
destroyed  by  the  gastric  juice.  As  a  rule,  previous  disease  leaves 
as  a  sequel  an  increased  disposition,  the  formerly  affected  tissues 


Acquired  Predisposition  and  Innnunify.  21 

sliowing  a  diminished  resistive  power  for  a  long  time  {local  pre- 
disposition; locus  ininoris  resistenticc),  as,  for  example,  mucous 
membranes  after  catarrhs. 

Predisposition  to  disease  and  (a  ^natter  of  extreme  impor- 
tance) immunity  against  disease  may  he  acquired.  It  is  well 
known  that  recovery  from  certain  infectious  diseases  is  accom- 
panied by  an  insusceptibility  to  a  repetition  of  the  same  affection. 
This  immujiity  after  previous  attacks  is  at  times  only  temporary, 
but  a  few  weeks  or  months  in  duration,  or  it  may  extend  over 
many  years  or  for  the  entire  lifetime.  The  alteration  which  has 
taken  place  in  the  condition  of  the  body  in  such  cases  is  chiefly 
a  chemico-biological  one,  and  although  much  remains  enigmatical 
concerning  it,  some  insight  into  the  process  has  been  obtained 
through  experimental  investigation.  Besides  the  discoveries  of 
Jenner  and  Pasteur,  who  gave  to  mankind  facts  and  methods  of 
the  highest  importance  toward  succe^  in  combating  infections, 
by  which  it  has  become  possible  by  artificial  inoculation  of  an 
attenuated  virus  to  produce  a  mild  course  of  the  infection  and  to 
obtain  therefrom  immvmity  from  subsequent  attacks  of  the  same 
disease,  there  must  also  be  recalled  the  important  discovery  that 
in  the  blood  of  man  and  animals,  after  attacks  of  infections,  there 
appear  certain  substances  which  are  of  specific  anti-toxic  char- 
acter and  are  destructive  to  the  virus,  and  that  upon  the  produc- 
tion of  these  substances  depend  protection  and  recovery  from  these 
diseases.  The  tissues  of  the  animal  body  react  to  irritants  which 
gain  access  to  them.  Should  a  particle  of  dust  or  a  gnat  happen 
to  lodge  upon  the  conjunctiva,  such  a  foreign  body  acts  as  a 
stimulant  to  the  nerves  of  the  mucous  membrane,  this  inducing  a 
free  secretion  of  tears,  which  usually  wash  away  or  dissolve  the 
object.  In  an  analogous  manner  there  is  a  reaction  on  the  part 
of  the  tissues  should  a  toxine  or  some  pathogenic  germ  (virus, 
bacterium)  come  into  contact  with  them,  not  in  this  case  with  a 
simple  secretion  to  wash  away  the  poison,  but  nevertheless  re- 
straining the  poison  and  giving  origin  to  substances  which  are 
apparently  actual  antitoxines,  or  which  are  able  to  destroy  and 
thus  render  harmless  the  germs  of  disease.  The  conditions  un- 
derlying the  production  of  such  antagonistic  or  protective  sub- 
stances, t^eir  mode  of  origin,  manner  of  action  and  properties,  are 
of  extremely  complex  nature.  The  numerous  experiments  of  such 
investigators  as  Behring,  Ehrlich,  Brieger,  Kitasato,  Wassermann, 
Buchner,  Emmerich,  Fodor,  Nuttall,  Nirssen,  Bordet,  Morgenroth 


22  Predisposition  and  Immunity. 

and  Sachs,  have,  however,  brought  forward  facts  hitherto  unsus- 
pected and  of  the  greatest  interest  in  this  connection,  and  have 
pointed  out  not  merely  theoretical  hypotheses  upon  immunity,  but 
also  practical  methods  of  extreme  value  in  combating  the  in- 
fectious diseases. 

As  already  pointed  out,  there  already  pre-exist  in  the  normal 
blood  of  every  animal  certain  substances  capable  of  dissolving 
foreign  material  which  has  in  some  way  gained  entrance,  and,  by 
entering  into  combination  with  resultant  toxic  matter,  of  render- 
ing it  harmless.  In  some  of  the  glands,  as  the  thyroid  and  liver, 
neutralization  of  toxic  matter  and  noxious  metabolic  products  is 
being  continually  carried  on ;  and  when  one  considers  the  innu- 
merable reactions  ;and  interactions  which  are  taking  place  in 
metabolism,  resulting  in  the  most  varied  types  of  secretory  ma- 
terial with  destructive  and  digestive  properties,  it  is  easy  to  think 
of  the  body  and  each  of  its  cells  as  a  chemical  laboratory  of 
manifold  productive  ability. 

In  attempting  an  explanation  of  the  m.echanism  involved  in 
the  production  of  these  antibodies  (antagonistic  or  protective 
substances),  Ehrlich  has  proposed  a  brilliant,  and,  at  first  thought, 
a  very  convincing  theory,  the  chief  points  of  which  are  briefly 
included  in  the  following.  The  hypothetical  details  of  this  theory 
have  recently  met  such  serious  objection  at  the  hands  of  Gruber 
that  in  a  great  measure  it  seems  but  doubtfully  credible.  The 
basic  fact  that  antitoxines  and  protective  substances  are  products 
of  the  cells  and  organs  of  the  body  is  not  endangered  by  this 
criticism,  but  the  problem  of  how  and  where  such  substances  are 
formed  is  renewed  as  a  matter  for  further  investigation. 

According  to  this  view  the  cells  of  the  body  may  be  thought 
of  as  organisms  which  consist  of  a  basis  of  protoplasm,  which 
has  as  its  vital  center  a  nucleus  (vital  nucleus  of  Ehrlich)  ; 
this  protoplasmic  unit  may  be  fancied  as  being  possessed  about 
its  periphery  of  armlike  processes,  the  receptors  or  side-chains  of 
Ehrlich.  [It  is  to  be  understood  here  that  the  author  refers  to 
the  protoplasmic  molecules  as  the  basis  of  this  theory,  each  mole- 
cule being  composed  of  a  more  or  less  complex  group  of  atoms 
or  of  combinations  of  atoms.  The  vital  center  does  not  refer  to 
the  nucleus  seen  as  a  structural  part  of  the  cell,  but  to  the  struc- 
tural nucleus  of  such  a  complex  molecule  of  its  protoplasm.  As 
is  attempted  in  the  graphic  chemical  formula  of  a  complex  or- 
ganic molecule  with  the  symbol    C    as    its    center,    to    indicate    as 


Ehrlich's  Theory  of  I  in  in  unity.  23 

"side-chains''  the  various  atoms  or  groups  of  atoms  linked 
about  this  nucleus,  so  in  Ehrlich's  view  the  living  proto- 
plasmic molecule  may  be  thought  of  as  having  as  its  elemental  or 
basic  compound  a  vital  nucleus  about  which  are  attached,  and 
probably  from  which  spring,  a  number  of  other  atomic  groups 
subsidiary  to  the  center  of  the  molecule  and  corresponding  to  the 
side-chains  of  the  formula,  but  essential  to  the  efficiency  and 
integrity  of  the  whole  complex  molecule,  since  they  are  its  means 
of  combination.  These  are  the  receptors  or  haptophores  of  the 
molecule.  Every  molecule  possesses  these  haptophores  in  addition 
to  its  principal  part,  the  centre  or  nucleus  (in  living  protoplasmic 
molecules,  the  vital  centre).  Should  these  haptophores  be  lost  in 
the  living  molecule,  they  are  replaceable  by  others  of  like  type 
because  of  the  vital  regenerative  power  of  the  molecule.] 

The  receptors  are  the  principal  instruments  of  [molecular,  or 
in  other  words]  intracellular  metabolism  and  provide  nutri- 
tive substance  to  the  cells  through  their  ability  to  unite  chemic- 
ally with  such  material.  However,  just  as  proper  food  elements 
may  thus  combine,  so  other  albuminous  bodies  or  materials  chem- 
ically allied  to  foods  become  linked  to  or  combined  with  the 
receptors,  as  material  extracted  from  bacteria,  various  poisons 
of  animal,  bacterial  and  vegetable  origin  (toxines,  venom  of  bees, 
spiders  or  snakes,  diphtheria  toxine,  ricin,  abrin,  the  substance 
of  blood  cells,  spermatozoa  and  nervous  tissue,  and  the  milk 
albumen  of  different  kinds  of  animals).  Such  union  occurs  be- 
cause these  substances  contain  in  their  molecular  composition 
certain  groups  of  atoms,  which,  like  similar  atomic  groups  in 
foods,  have  an  affinity  (chemical  affinity)  for  the  atomic  groups 
of  the  cellular  protoplasm ;  these  Ehrlich  speaks  of  as  their 
haptophore  groups.  [Thus  both  the  protoplasmic  molecules  of 
the  body  cells  are  provided  with  haptophores  or  combining  chains, 
and,  too,  all  nutritive  or  harmful  molecules  which  come  in  con- 
tact with  them.  Should  there  be  affinity  between  the  haptophores 
of  the  cellular  protoplasm  and  those  of  the  introduced  molecules  a 
combination  will  result.]  With  such  combination  effected 
[the  molecule  and  in  proportionate  degree  the  whole]  cell  comes 
under  the  influence  of  the  substance  chained  to  it.  Should 
the  latter  possess  properties  actively  harmful  to  the  protoplasm, 
poisonous  qualities  (toxophorc) ,  the  cellular  protoplasm  becomes 
more  or  less  injured,  and  a  pathological  cellular  lesion  results. 
There    may    ensue    complete    death     of    the     cell     [protoplasm], 


24  Predisposition  and  Immunity. 

or  merely  a  condition  of  irritability  or  partial  injury.  If  the 
injury  be  partial  tliat  part  of  the  cell  [protoplasmic  molecule] 
which  remains  sound  restores  the  defect.  In  this  condition  of  irri- 
tability or  stimulation  there  is  a  reaction  on  the  part  of  the  cellular 
protoplasm  left  with  its  vital  centre  intact  to  regenerate  the 
receptors  destroyed  by  the  toxic  influence.  Following  a  law 
recognized  by  Weigert,  regeneration  in  the  cells  of  an  organism  is 
usually  productive  of  more  of  the  substance  than  originally  ex- 
isted at  the  site  of  loss ;  and  so  here  the  restoration  is  often  so 
active  that  an  excessive  number  of  receptors  are  supplied  to 
replace  those  which  have  been  destroyed.  "Such  an  excess  of 
receptors  constitutes  a  useless  ballast  for  the  cells  and  the  extra 
ones  are  thrown  out  into  the  blood  and  circulate  therein"  (Ehr- 
lich,  Wechsberg).  The  presence  of  these  free  receptors  in  the 
blood,  representing  haptophores  or  chemically  combining  sub- 
stances, affords  opportunity  for  materials  which  have  gotten  into 
the  blood  and  which  have  chemical  affinity  for  them,  having  come 
in  contact,  to  enter  into*  combination  with  the  receptors.  Thus 
held  by  these  free  receptors,  such  substances  are  prevented  from 
involving  the  cellular  protoplasm,  and  as  a  result  the  cells  and 
the  whole  individual  are  protected  from  the  disease. 

This  power  of  molecular  combination  differs  in  the  different 
cells  of  the  same  individual  and  in  the  cells  of  different  species 
of  individuals.  One  species  may  possess  no  cells  containing  the 
elements  essential  for  combining  with  a  certain  toxine;  there 
would  then  be  absolutely  no  chemical  affinity  shown  between  the 
cellular  molecules  and  the  toxic  molecules,  and  a  priori  the  latter 
must  be  without  effect.  In  such  a  case  the  toxine,  perhaps  in 
large  quantities,  may  remain  for  weeks  in  the  blood  and  general 
circulation  without  any  harm  resulting  to  the  individual.  Such 
instances  are  examples  of  natural  immunity.  On  the  other  hand, 
an  individual  may  possess  a  vast  number  of  receptors  not  merely 
in  the  general  body,  but  each  cell,  each  corpuscle,  for  example, 
may  contain  a  mass  of  material  capable  of  combining  with  sub- 
stances of  one  or  other  kind.  In  classification  of  these  receptors 
it  is  customary,  following  Ehrlich,  to  distinguish  them  as  of 
I,  II,  III,  etc.,  orders. 

The  first  order  (unieeptors)  includes  receptors  having  only 
one  haptophore  group  for  poisons  (toxines)  and  utilizing  this  for 
combination  with  such  substances ;  they  are  called  antitoxines. 
The   presence  and   formation   of   antitoxines   is   illustrated   by   the 


Lysiiis.  25 

immunity  to  toxines  acquired  after  infectious  disease.  The  tox- 
ines  are  allied  to  the  albumens*  and  enter  the  blood  in  a  state  of 
solution ;  thus  dissolved,  they  here  enter  into  combination  and  are 
therefore  inert  before  they  gain  access  to  the  tissues,  as  the  nerv- 
ous tissues — the  cells  (bacteria)  which  give  origin  to  the  toxines 
being  removed  from  the  economy  by  phagocytosis  (as  tetanus  or 
diphtheria  bacilli). 

Another  class  of  receptors  [III  order  of  Ehrlich]  has  the 
power  of  combining  with  foreign  cellular  elements  and  at 
the  same  time  drawing  into  the  combination  the  ferment-like 
alexines  which  naturally  have  pre-existed  in  the  blood ;  these 
thus  must  possess  two  haptophore  groups  (a  cytophile  and  a 
complementophile  group),  and  for  this  reason  are  known  as 
amboceptors.  For  this  element  which  is  the  medium  (amboceptor) 
of  the  chemical  union  (anchoring  together)  the  following  terms 
are  also  employed:  dcsiiwji  (se'w  :=  I  bind),  immune  body, 
intermediary  body,  copula,  immunisin,  fi.vateur,  sensitising  body. 
The  alexine  is  also  known  as  the  complement,  addiment  and 
cytosc.  \\'hen  by  the  combined  action  of  these  two  elements  the 
destruction  and  solution  of  foreign  cellular  elements  (the  toxine- 
producing  animal  and  vegetable  microorganisms  themselves)  are 
accomplished,  the  compound  antibody  [amboceptor  and  comple- 
ment] is  spoken  of  as  a  cytolysin  (E.  S.  London).  The 
presence  of  the  two  elements  allied  to  each  other  is  shown  by 
experiment.  If  one  will  heat  a  serum  containing  cytolysins  to 
56°  C.  the  complemental  element  will  be  destroyed,  and  the 
serum  will  be  fovmd  to  have  lost  its  cytohtic  power,  is  inert.  If, 
however,  to  this  serum  there  be  added  another,  ordinary  serum, 
containing  only  complement  and  inert  by  itself,  the  cytolytic 
power  is  restored  to  the  first,  and  it  is  said  to  have  been 
reactivated.  So,  too,  the  desmon  or  amboceptor  in  the  c}i;olysin 
may  be  removed  by  adding  to  serum  cells  for  which  it  has 
affinity  [and  by  centrifugation  these  may  be  thrown  down :  while 
the  serum  continues  to  contain  the  complement] .  There  are 
a  number  of  cytolysins  of  different  kinds,  each  exerting  its 
influence  as  a  rule  upon  only  one  certain  kind  of  cell  [this 
depending  upon  the  peculiar  affinity  of  the  amboceptor  in  the 
cvtolvsin  combination]  :  thus  we  recognize  amongf  manv 
those  which  act  upon  red  blood  cells   (hccmolysins) ,  upon  sperma- 

♦Poisons  of  other  types,  alkaloids,  glucosldes.  saponines,  which  do  not  act  by 
forming  chemical  combination  do  not  cause  the  formation  of  antitoxines  In  the 
organism.      (Ehrlich,  H.  Sachs.) 


« 


26  Predisposition  and  Immunity. 

tozoa  (spermolysins) ,  upon  bacteria  (bacteriolysins) ,  upon  white 
blood  cells  (leucolysins).  Some  dissolve  several  kinds  of  cells,  as 
in  the  case  of  spermolysins,  which  destroy  red  blood  cells  as  well 
as  spermatozoa.  From  this  it  may  be  seen  that  in  general 
cytolysins  possess  specificity  of  action. 

The  appearance  of  cytolysins  in  the  body  of  any  given  animal 
is  occasioned  by  the  introduction  of  cells  of  a  different  species  of 
animal  into  the  first.  If  human  blood  be  injected  in  increasing 
amounts  under  the  skin  of  a  rabbit  or  into  its  peritoneum,  the 
serum  of  the  rabbit  will  acquire  the  power  of  dissolving  the  hu- 
man red  blood  cells,  but  not  those  of  horses,  cattle  or  guinea-pigs. 
If  the  spermatic  fluid  of  guinea-pigs  be  introduced  into  rabbits, 
in  the  same  way  the  serum  of  rabbits  becomes  solvent  for  the 
spermatozoa  of  guinea-pigs,  but  cannot  influence  the  spermatozoa 
of  another  species  of  animal.  If  colon  bacilli  be  injected  into  an 
animal  a  cytolysin  will  be  developed  destructive  only  to  these 
microphytes,  and  in  fact  only  to  the  particular  strain  of  this 
bacterial  group  which  was  employed  in  the  experiment. 

From  the  foregoing  it  should  be  reahzed  that  the  principal  feature 
in  the  production  of  immunity  against  foreign  celhtlar  elements  is  the 
formation  of  the  amboceptor  or  desmon,  and  that  this  alone  is  a  new 
product  of  the  cells  of  the  invaded  body ;  the  other  element,  the  alexine, 
naturally  pre-exists  in  every  body,  its  combination  with  the  desmon  form- 
ing the  cytolysin.  If,  however,  the  necessary  alexine  be  absent  or  present 
in  insufficient  amount,  the  C3'tolysin  will  not  appear.  In  this  latter  way  must 
be  explained  such  occurrences  as  where,  in  spite  of  repeated  introduction 
into  an  animal  of  some  type  of  cells,  the  blood  acquires  no  cytolytic  power, 
but  where  on  further  addition  of  the  serum  (containing  the  required  alex- 
ine) from  another  species  of  animal  cytolytic  activity  is  immediately 
produced. 

The  sources  of  the  amboceptors  are  apparently  the  bone- 
marrow,  spleen,  lymph  glands  and  perhaps  the  subcutaneous  con- 
nective tissues. 

In  addition  to  the  production  of  antitoxic  and  cytolytic  sub- 
stances the  body  may  engage  along  the  same  line  of  reaction 
in  the  formation  of  substances  [II  order  of  Ehrlich]  which 
cause  foreign  cells  to  aggregate  in  masses  (clumping,  agglutina- 
tion), the  so-called  Agglutinins;  and  other  substances  which 
coagulate  foreign  types  of  albumens  (Coagulins)  and  cause  their 
precipitation  (Precipitins).  In  illustration,  if  defibrinated  human 
blood  be  injected  into  a  rabbit  there  is  developed  in  the  blood 
of   the    latter    a    substance    which    will    act    on    human    blood    to 


Post-Infections  Immunity.  27 

cause  a  flocculent  precipitate.  Init  which  will  not  (as  a  rule,  and 
never  if  certain  m(3des  of  application  are  employed)  exhibit  such 
precipitating^  qualities  with  any  other  type  of  blood.  It  is  inter- 
esting in  this  connection  to  add  that  the  serum  of  a  rabbit  so 
treated  will  also  precipitate  the  blood  of  anthropoid  apes,  gorillas, 
orang-outangs  and  chimpanzees,  thus  indicating  a  relationship  of 
these  animals  to  man.  Cytolysins  and  haemolysins  also  serve  to 
show  the  relationships  existing  between  animals  in  the  zoological 
system  of  classification.  Inasmuch  as  this  reaction  is  applicable 
as  well  with  a  solution  of  old  and  dried  blood,  the  discovery 
(which  as  an  outcome  of  research  in  the  field  of  immunity  is  due 
particularly  to  Bordet,  Ehrlich  and  Morgenroth)  has  acquired 
especial  importance  as  a  means  of  information  concerning  the 
source  of  blood  stains  in  forensic  medicine. 

Other  albumens  may  also  lead  to  the  formation  of  specific 
antibodies  in  the  animal  organism,  as  milk  albumen ;  thus  by 
subcutaneous  injection  of  goat's  milk  into  rabbits,  horses  or  cows 
a  serum  may  be  obtained  which  wilt  immediately  cause  a  precipi- 
tate if  it  be  added  to  goat's  milk.  In  the  same  way,  by  inocula- 
tion, coagulins  may  be  obtained  for  cow's  milk. 

In  the  same  way,  too,  in  the  course  of  an  infectious  disease 
a  series  of  substances  are  produced  in  the  human  or  ani- 
mal organism  which  render  the  infectious  matter  for  the  time 
harmless.  Should  the  infectious  products  develop  very  rapidly, 
and  by  their  poisonous  properties  cause  serious  protoplasmic 
changes  in  the  bodv  cells,  the  disturbance  is  apt  not  to  be  limited 
or  checked,  and  in  spite  of  any  reactive-products  which  may  be 
formed  the  function  of  the  cells  becomes  altered  and  the  animal 
dies.  Should  the  [protoplasmic  molecules  of  these]  cells  be  only 
partly  injured  the  body  prevails  over  the  disease,  the  molecular 
defects  of  the  cells  becoming  regenerated.  The  surplus  of  anti- 
bodies, the  result  of  this  regenerative  action,  are  after  recovery 
found  circulating  in  the  blood,  and  in  some  instances  may  even 
pass  into  the  milk.  The  amount  of  protective  bodies  or  anti- 
bodies in  the  body-fluids  varies  according  to  the  intensitv  of  the 
reaction  and  the  time  elapsed  after  recovery  from  the  infection, 
the  greater  part  being  used  up  during  the  course  of  the  disease 
and  the  remaining  gradually  disappearing  in  metabolism ;  while 
with  the  removal  of  the  stimulus  the  supply  from  the  cells  tends 
to  cease.  If,  however,  infectious  and  toxic  material  be  again 
introduced  into  the  system,   stimulating  and  injuring  the  cellular 


28  Predisposition  and  Immunity. 

protoplasm,  the  production  of  antibodies  will  be  again  induced, 
receptors  being  again  formed.  This  form  of  immunity,  produced 
through  cellular  activity  following  the  introduction  of  the  infec- 
tious agents,  is  known  as  "'active  immunization."  The  discovery 
of  the  existence  and  production  of  specific  antibodies  in  the  serum, 
for  which  we  are  mainly  indebted  to  the  studies  of  Behring  upon 
tetanus-  and  diphtheria-immunity,  has  led  to  extremely  im- 
portant methods  of  prophylactic  and  therapeutic  inoculation  against 
a  number  of  the  infectious  diseases.  This  becomes  possible  from 
the  fact  that  the  blood*  serum  of  an  animal  which  has  survived  a 
certain  infection  and  is  highly  immunized  against  it  can  be  em- 
ployed by  injection  to  produce  in  a  second  animal  similar  im- 
munity against  the  same  disease.  The  production  of  the  pro- 
tective material  in  the  blood  depends  upon  the  introduction  into 
the  experiment  animals,  either  intravenously  or  subcutaneously,  of 
gradually  increasing  amounts  of  the  infectious  material  against 
which  immunization  is  sought.  The  animals  in  this  way  become 
more  and  more  highly  immunized  and  their  blood  serum  becomes 
correspondingly  rich  in  antitoxine.  By  such  a  system  of  pro- 
gressive inoculation  it  is  possible  to  attain  a  degree  of  concentra- 
tion in  which  a  thimbleful  of  the  serum  contains  more  immuniz- 
ing material  than  would  exist  in  all  the  blood  of  the  body  after 
one  single  attack  of  the  disease.  The  ability  to  produce  such 
materials  exists  in  the  cells  of  all  kinds  of  animals,  both  those 
susceptible  to  the  disease  in  question  and  those  naturally  resistant 
to  it.  For  example,  by  injecting  the  bacilli  of  swine-erysipelas, 
which  in  natural  conditions  are  pathogenic  only  to  the  bristled 
kine,  it  is  possible  to  induce  the  reaction  also  in  sheep,  goats, 
cattle  and  horses  and  produce  in  their  blood  immunizing  substances ; 
and  then,  after  withdrawal  of  the  blood  from  animals  thus  pre- 
pared, to  obtain  from  it  a  prophylactic  and  curative  serum  in  suffi- 
cient quantity  for  use  in  hogs.  The  production  of  active  im- 
munity in  an  individual  requires  some  time,  because  the  body  cells 
must  first  form  the  protective  substances ;  in  other  words,  must 
first  pass  through  the  period  of  the  disease,  perhaps  four  to  six 
weeks  in  duration.  \A'hen,  however,  the  prepared  serum  is  intro- 
duced there  is  no  such  demand  placed  on  the  body  cells ;  the  pro- 
tective substances,  already  formed,  produced  from  the  animal 
supplying  the  serum  are  introduced  into  the  second  animal.  An 
immunity  thus  obtained  is  spoken  of  as  "passive  immunity."  It 
comes   on   immediately   or   in   a   few   hours   after   the   inoculation. 


Protective  Immunization.  29 

according  to  circumstances.  As  a  definite  cellular  reaction  in 
such  a  case  does  not  occur  at  all,  or  at  best  only  in  a  minor 
degree,  and  as  the  amount  of  protective  antitoxic  material  intro- 
duced is  gradually  used  up,  destroyed  or  excreted  ,  (urine)  and 
no  new  antitoxine  is  afforded  because  of  lack  of  proper  reaction, 
such  passive  immunity  passes  away  after  a  short  time  (seven  to 
fourteen  days). 

The  recognition  of  this  peculiarity  has  in  practical  application 
led  to  ,  the  coincident  or  successive  employment  of  both  methods 
of  immunization  in  case  of  certain  of  the  infectious  diseases. 
Serum  is  first  injected  so  as  to  induce  a  passive  immunity  in  an 
animal,  and  living  germs  are  next  inoculated  so  as  to  transfer  a 
passive  into  an  active  immunity ;  the  previous  introduction  of  the 
protective  serum  making  the  later  inoculation  with  living  microbes 
practically  free  from  danger. 


CONGENITAL  AND  INHERITED  DISEASES 

If  there  exist  at  time  of  birth  in  an  individual  actual  disease, 
or  peculiarities  of  predisposition  or  immunity  which  also  char- 
acterized the  parents  or  ancestors,  such  conditions  are  said  to  be 
congenital  (innate),  and  in  the  latter  instance  inherited  (heredi- 
tary) as  well.  The  genesis  of  such  an  occurrence  is  by  no  means 
always  the  same,  although  in  a  measure  it  is  apparently  dependent 
upon  conditions  of  the  parents. 

During  intrauterine  life  the  embryo  may  experience  injuries 
affecting  its  normal  growth,  causing  deformity,  interfering  with 
the  proper  development  of  a  limb  or  organ,  or  destroying  some 
part  already  in  stage  of  development.  Such  injuries  are  for  the 
most  part  mechanical  in  type,  as  where  amniotic  adhesions  (or 
more  rarely  tumors  of  the  uterus)  by  constriction  or  pressure  of 
this  or  that  part  of  the  foetus  (which  in  its  movements  might  be 
entangled  in  the  amnion)  may  compress,  wound  or  otherwise 
injure  it.  Depending  on  the  nature  of  such  an  injury,  the  embryo 
may  in  consequence  present  gross  or  trivial  faults  of  one  sort  or 
another;  these  are  spoken  of  as  foetal  or  emhryogenous  anomalies, 
Z'itia  congenita,  developmental  defects  or  monstrosities.  Except 
when  a  uterine  lesion  is  the  cause  of  the  deformation  of  the  foetus, 
the  mother  has  no  influence  upon  the  production  of  anomalies  in 
the  offspring. 

There  are  a  number  of  infectious  diseases  whose  causative 
micro-organisms  are  capable  of  gaining  access  to  the  foetus  indi- 
rectly through  the  placenta.  In  .their  multiplication  in  the  pla- 
cental tissue  they  may,  by  growth,  penetrate  it  and  obtain  entrance 
to  the  blood  of  ,  the  foetal  side.  Under  such  circumstances  the 
newly  born  animal  carries  into  the  world  with  it  the  same  disease 
from  which  the  maternal  parent  was  sufferinig  during  the  term  of 
her  pregnancy;  the  acquirement  is  here  placental.  The  most  com- 
mon example ,  of  such  a  transmission  is  seen  in  congenital  tuber- 
culosis in  cattle,  occurring  only  in  case  the  cow  has  uterine  tuber- 
'culosis.     The  congenital  pathological  conditions  of  this  type  have 


Congenital  Predisposition.  31 

therefore  an  intrauterine  mode  of  origin,  which,  if  strictly  niter- 
preted,  is  comparable  to  acquirement  by  an  external  influence,  only 
tliat  in  this  instance  it  operates  within  the  womb. 

It  is  reasonable  to  believe  that  injurious  metabolic  products 
which  pass  through  the  placenta  of  a  mother  animal  suffering 
from  some  febrile  condition  (especially  metabolic  and  nutritive 
disturbances  which  react  from  the  mother  upon  the  embryo, 
affecting  primarily  the  ovum,  or  in  the  father's  case  affecting  the 
spermatozoon  in  a  similar  manner)  occasion  morbid  predisposi- 
tions, as  diminished  developmental  energy,  or  perhaps  a  tendency 
to  excessive  growth  (dwarfism,  fcetal  chondrodystrophy,  gigan- 
tism), weak  metabolic  power,  tendency  to  fatty  degeneration  or 
fatty  deposition  {ovo genie  or  spermatogenie  predisposition,  con- 
genital degenerative  inheritance). 

According  to  Weissmann  and  Ziegler,  it  is  quite  probable  that 
often  predisposition  to  disease  and  congenital  pathological  char- 
acteristics are  due  to  germinal  variations;  that  is,  that  when  two 
unadapted  sexual  cells  unite  there  may  be  developed  to  some  de- 
gree new  and  perhaps  even  abnormal  peculiarities  in  the  embryo 
from  the  union  of  the  two  elements  (amphimixis  of  the 
ovum  and  spermatozoon).  Thus  healthy,  strongly-constituted 
parents  may  often  be  seen  who  sometimes  beget  offspring  of 
feeble  constitution,  weak-minded  or  of  other  morbid  tendency. 
The  off'spring  is  never  entirely  like  either  parent,  and  the  various 
members  of  the  same  generation  are  never  alike  in  bodily  struc- 
ture and  character.  Only  in  case  of  twins,  developing  from  one 
ovum  or  from  one  act  of  copulation,  is  there  striking  similarity  of 
the  bodily  features.  In  the  mingling  of  the  maternal  and  paternal 
sexual  elements  two  strains  of  hereditary  tendency  unite  to  pro- 
duce new  germinal  variations.  Should  there  be  thus  produced 
new  peculiarities  of  value  to  the  individual,  or  which  we  care  to 
preserve,  type-characteristics  (precocity),  these  are  not  regarded 
as  pathological ;  but  it  is  readily  conceivable  that  the  variations 
might  but  poorly  fit  the  off'spring  for  life  and  render  it  but  feebly 
resistant  to  given  pathogenic  influences  or  show  from  the  first 
abnormal  constitution  of  its  tissues.  In  such  cases  is  presented  a 
germinative  or  constitutional  predisposition. 

A  predisposition,  no  matter  how  developed,  as  well  as  ac- 
quired immunity,  may  be  transmitted  to  the  offspring,  provided 
the  individual  is  capable  of  begetting;  yet  not  every  tendency 
toward  disease  and  not  all  the  resistive  powers  of  the  parent  are 


32  Heredity. 

necessarily  continued  to  succeeding  generations.  Only  such  con- 
ditions are  transmitted  as  pre-existed  in  the  germ,  in  the  seg- 
mentation cells  and  the  embryo,  or  those  in  which  apparently  the 
nature  of  the  whole  parental  cellular  structure  is  altered,  as 
germinal  variations  and  so-called  constitutional  tendencies  and 
diseases. 

Injuries  and  diseases  which  do  not  involve  the  sexual  cells,  as 
all  simple  traumatic  lesions  of  the  body,  give  rise  to  no  trans- 
mission. For  example,  the  common  custom  of  cropping  the  ears 
and  tails  of  dogs  has  never  led  to  the  birth  of  a  short-eared  or 
stub-tailed  dog  or  of  such  a  breed  (just  as  the  practice  of  cir- 
cumcision, practiced  for  hundreds  of  years  among  various  peo- 
ple^ has  never  yet  caused  any  congenital  anomalies  of  the 
prepuce).  If  occasionally  structural  anomalies  of  this  type  are 
encountered  careful  investigation  will  show  that  some  intrauterine 
mechanical  fault  is  responsible  for  the  defect  in  the  foetus,  as 
Bonnet  has  demonstrated  in  case  of  stump-tailed  dogs  that  the 
caudal  vertebrae  have  been  bent  or  deformed  simply  by  intra- 
uterine pressure  (amnion).  This  is  also  proved  by  the  fact  that 
the  same  anomaly  occurs  in  cats  (and  in  any  other  animals  whose 
tails  are  unobjectionable  to  man  and  for  the  removal  of  which 
there  is  no  occasion),  showing  that  the  habit  of  cropping  can 
scarcely  be  held  responsible. 

Non-transmissible  conditions  and  those  which  are  truly  in- 
herited may  very  closely  resemble  each  other  in  their  anatomical 
features,  and  yet  depend  on  entirely  different  causes ;  only  the 
closest  inquiry  revealing  the  fundamental  influences  producing 
them.  For  example,  supernumerary  toes  (polydactylism)  may  be 
an  atavistic  phenomenon,  a.  family  trait,  or  may  occur  in  a  foetus 
as  a  splitting  of  a  digit  because  of  amniotic  adhesions ;  in  the 
same  way  harelip  (congenital  fissure  of  the  Ijp)  may  be  caused 
by  local  amniotic  trauma  or  may  be  an  hereditary  anomaly. 

Heredity  is  best  understood  when  it  concerns  chemical  in- 
Hucnces.  As  indicated  by  Ribbert,  it  may  be  conceived  that  the 
whole  bodv  can  suffer  from  the  wide  dissemination  through  it  of 
some  chemical  substance  and  that,  of  course,  under  the  circum- 
stances the  germ  cell  is  also  reached  by  the  same  noxious  ma- 
terial. If  the  organism  survive  such  disturbance  and  become 
immune  through  the  changes  called  forth  by  the  chemical  poison, 
the  germ  cell  may  also  survive  with  the  same  iniinitiuciiig  changes. 
Should    such   a   process    befall    both    parents,    both    spermatozoon 


Hereditary  Disease.  '  33 

and  ovum  are  likely  to  be  imnuine  and  the  new  cellular  structure 
resulting  from  the  copulation  of  these  two  (the  embryo)  will 
possess  the  same  characteristic  and  transmit  it  again,  because 
its  own  sexual  cells  are  clearly  the  descendants  of  the  rest  of 
the  group.  In  the  same  way  a  predisposition  may  be  established 
and  transmitted,  because  the  chemical  substance  in  some  way 
weakens  the  germ  cell  and  diminishes  its  resistive  ability,  and  by 
the  fusion  of  two  similarly  enfeebled  sexual  cells  the  progeny,  as 
the  product  of  both,  partakes  of  their  equalities.  Similarly  to 
such  chemical  influence  as  Ribbert  suggests,  any  exaggeration 
or  diminution  of  the  body  temperature  must  affect  the  germ 
cells. 

Inherited   pathological   conditions   and   properties   of   immunity 
need  not  necessarily  manifest  themselves  in   each  successive  gen- 
eration   of    posterity    indefinitely;    for    the    most    part    they    are 
limited  to  a  few  generations  and  then  disappear.     But  they  may 
recur  in  later  generations.     If  but  one  of  the  progenitors  possess 
a  certain  predisposition  and   come   in  sexual   union   with   a   non- 
predisposed   individual,    the    pathological   condition    will   progress- 
ively  diminish   by   half    (Ribbert)    because   of   its    distribution    in 
the  two  sexual  cells ;  is  proportionately  corrected  by  the  healthy 
cell    of    the    copulation    and    by    germinal    variation ;    and    grows 
weaker  and  weaker  until  it  is  no  longer  a  factor  in  the  posterity. 
Should  the  peculiarity  reappear  after  several  intervening  genera- 
tions, it  may  be  assumed  that  this  occurs  as  a  result  of  the  union 
of   two   germ    cells,    each    possessed   beforehand    of   a    disposition 
which  was  hitherto  latent,  but  which  from  the  summation  of  the 
characteristics   of  both  parent   cells   has  again  become   sufficientlv 
intensified  to  reappear  as  a  pathological  fault  (Ribbert).    Hence  we 
distinguish:  a  direct  li credit y  from  father  and  mother  to  the  oiT- 
spring;  a  latent  heredity  if  the  offspring  of  affected   parents  are 
spared  but  in  the  next  or  later  generations  the  disease  should  appear, 
arising  from  a  transmitted  tendency ;  a  collateral  heredity,  should 
the  disease  manifest  itself  in  the  side  lines  of  the  family  group ; 
an  atavistic  heredity,  when  the  origin   of  the  disease   suggests  a 
reversion  to  the  family  ancestry. 

In  human  medical  practice  the  following  are  considered  as 
diseases  transmissible  by  heredity:  Hsemophilia  or  hsemorrhagic 
diathesis,  color  blindness  or  Daltonism  (so  named  after  the 
Englishman,  Dalton,  who  was  himself  color-blind),  lenticular 
opacity    or    "gray    cataract"     (or    cataract),    near-sightedness    or 


34  Heredity. 

myopia,  pigment-atrophy  of  the  retina,  polyuria  (production  of 
excessive  amounts  of  urine),  predisposition  to  mental  diseases,  to 
progressive  muscular  atrophy,  to  tumors,  to  obesity  and  to  cer- 
tain malformations  (dwarfism,  polydactylism,  harelip,  etc.).  The 
anomalous  conditions  mentioned  are  due,  perhaps,  to  germinal 
variations,  possibly  first  brought  into  active  manifestation  by 
the  introduction  of  some  external  disturbing  factor.  (Vide  Rib- 
bert,  Lehrbn'ch  der  all  gem.  Pathologie.     1901.) 

What  parts  respectively  are  taken  by  heredity  and  by  external 
influences  in  the  development  of  congenital  affections  is  in  many 
instances  difficult  or  even  impossible  to  determine,  as  our  knowl- 
edge of  these  matters  is  still  deficient.  This  is  particularly  true 
regarding  the  so-called  hereditary  defects  of  the  domestic  animals. 
Among  the  diseases  included  in  this  category  for  the  last  century 
or  more,  some  are  surely  not  inherited  and  not  transmissible  but 
occur  because  of  external  influences ;  for  example,  intermittent 
ophthalmia,  cataract,  asthma,  ringbone,  frog-thrush.  Others,  as 
dumb-staggers  ["blind-staggers"],  hsemoglobinsemia,  curb,  spavin, 
deficient  hoof-formation,  may  be  caused  directly  by  external  in- 
fluences, although  it  cannot  be  denied  that  inherited  structural  de- 
fects may  indirectly  favor  their  appearance.*  As  instances  of 
direct  inheritance  and  congenital  origin  may  be  mentioned  many 
cases  of  goitre  in  animals. 

*Cf.  Dleckerhoff.  Veher  d.  Erhfehler  hei  Zuchtpferden:  Zcitschr.  f.  Vctcrinar- 
hunde,  1902,  Feb.,  p.  53. 


CAUSES    OF    DISEASE 

The  influences  Avhich  lead  to  bodily  injury,  to  pathological 
lesions,  and  which  are  spoken  of  collectively  as  disease  causes 
(causer  uwrhi)   may  be  arranged  in  a  number  of  classes. 

There  are  influences  dgainst  which  the  strongest  and  most 
resistive  constitution  is  powerless  and  which  inevitably  induce 
disease  in  the  animal  coming  under  their  action ;  such  absolute 
pathogenic  influences  include  mechanical  forces,  intense  thermic 
and  electric  agencies,  mineral  and  vegetable  poisons  in  their 
higher  dosage  and  concentration,  and,  provided  they  can  gain 
entrance  to  the  intracorporeal  structures,  various  animal  para- 
sites, bacteria  and  [animal]  microorganisms.  Other  harmful 
agencies  are  pathogenic  only  under  special  circumstances  and 
are  therefore  only  relative,  depending,  for  example,  on  the 
quantity  of  the  exciting  agent,  or  upon  special  predisposi- 
tion of  the  subject  or  upon  the  concurrence  of  several  harmful 
influences  {relative  causes  of  disease).  The  occasion  which  brings 
a  harmful  influence  in  relation  with  the  body  or  subjects  the 
latter  to  such  influence,  is  spoken  of  as  the  predisposing  cause 
(causa  proximo).  The  principal  factor  in  producing  a  lesion  is 
known  as  the  special,  immediate  or  essential  cause  of  disease 
(causa  essentialis)  ;  among  these  it  should  be  understood  that 
either  external  harmful  agencies  which  have  gained  entrance  into 
the  body  or  which  operate  upon  it  from  without,  or  some  already 
existing  tendency  toward  disease  may  be  included.  For  example, 
pasturing  upon  some  upland  infested  with  anthrax  affords  the 
opportunity  by  which  the  anthrax  bacillus  as  the  essential  cause 
of  anthrax  gains  entrance  to  the  body ;  an  injury,  the  favoring 
condition  for  wound  infection  by  the  essential  cause  of  tetanus. 
Anything  which  promotes  the  action  of  an  injurious  agent  may 
be   regarded  as  a   contributary  cause    (causa  auxilians). 

Pathological  influences  may  be  divided  into  the  following 
groups : 


36  Causes  of  Disease. 

1.  Disturbances  of  Nutrition  and  Alimentation:  Abnormal 
states  of  nutrition  depending  on  irregularity  in  the  water  or  nutri- 
tive elements  afforded. 

2.  Obstructions  to  Respiration:  Interferences  with  oxygen 
convection. 

3.  Functional  Disturbances:  Depending  upon  fatigue,  upon 
overexercise  of  the  organs. 

4.  Thermic   Influences:     High    or   low   temperatures. 

5.  Electric  Agencies. 

6.  Mechanical  or  Traumatic  Agencies. 

7.  Chemical  or  Toxic  Agents:     Poisons. 

8.  Microbic  or  Infectious  Agents:  Micro-organisms  belong- 
ing to  the  protopbytes  and  protozoa. 

9.  Animal  Parasites:     Of  the  class  of  worms  and  arthropoda. 

Disturbances    of    Alimentation    and    Nutrition. 

Total  deprivation  of  food  without  water  supply  (complete  in- 
anition) leads,  in  case  of  the  higher  vertebrates,  to  rapid  loss  of 
bodv-weight.  emaciation  and  death  in  the  course  of  from  one  to 
four  weeks.  A\'ith  absolute  rest  (as  in  case  of  imprisonment  in 
a  caved-in  mine)  an  adult  man  may  retain  life  without  food  and 
drink  for  about  twenty  days :  exertion  hastens  the  end.  Strong 
dogs  have  lived  under  similar  conditions  for  thirty-six  days ; 
horses  and  cats  should  live  for  about  four  weeks  with  absolute 
rest.  Guinea-pigs  and  rats  die  within  three  to  nine  days.  Liberge 
states  that  a  well-conditioned  cow.  which  had  wandered  into  an 
out  of  the  way  place  and  had  remained  there  forty  days  without 
food  and  without  opportunity  for  much  exercise,  picked  up 
quickly  on  a  milk  diet  and  was  in  tolerable  condition  eight  days 
after  being  set  free. 

If  water  is  obtainable  abstinence  from  food  can  be  endured 
without  permanent  harm  by  man  and  carniverous  animals  for 
from  two  to  four  weeks,  and  the  fatal  end  may  be  postponed  for 
a  considerably  longer  period.  A  cat  experimented  on  by  Bidder, 
weighing  two  and  one-half  kilograms,  died  on  the  eighteenth  day 
from  star\-ation  after  having  lost  1,197  grams  (water  consumed, 
131. 5  grams).  Birds  of  prey  (eagle)  endure  hunger  and  thirst 
for  twenty  to  twenty-eight  days;  small  birds  only  two  to  nine 
days,  rvlascagni  has  recorded  a  turkey's  having  fasted  for  twenty- 
nine  days.  In  case  of  cold-blooded  animals  the  requirement  for 
food  is  so  small  that  water-salam.anders  and  turtles  mav  live  for 


Disturbances  of  Nutrition.  37 

a  year,  snakes  for  six  months  and  frogs  for  nine  months,  taking 
nothing  but  water. 

When  fasting  an  animal  must  furnish  whatever  energy  is 
necessary  for  the  maintenance  of  its  proper  temperature  and  for 
its  organic  functions  (muscular  activity  and  circulation)  by  the 
destruction  of  its  body  tissues,  nourishment  from  external  sources 
being  impossible  or  insufficient.  How  the  destruction  of  tissues, 
an  actual  self-combustion,  takes  place  and  how  the  vital  organs 
live  upon  the  less  important  structures,  is  well  shown  by  the  com- 
prehensive studies  of  E.  Voit.  Fat  and  glycogen  are  first  sacri- 
ficed, and  as  long  as  these  substances  are  present  the  albuminous 
elements  are  not  subject  to  the  destructive  process,  the  muscular 
structures  afterwards  bearing  the  greatest  part  of  the  loss.  Loss  of 
weight  and  atrophy  are  most  marked  in  the  omentum  and  the 
fleshy  parts  (also  the  fat  and  glycogen  stored  in  the  liver),  and 
fat  animals  succumb  to  starvation  later  than  lean  ones  Accord- 
ing to  Chossat,  young,  poorly  nourished  pigeons  die  after  three 
days  with  a  loss  of  one-third  their  body-weight ;  plump  ones  after 
thirteen  days,  with  a  loss  of  half  their  weight.  The  heart  shows 
the  least  loss  in  weight  (its  constant  activity  and  functional  stimu- 
lation hindering  its  atrophy)  ;  the  central  nervous  system  similarly 
loses  but  little,  and  the  diminution  in  the  red  corpuscles  is  com- 
paratively unimportant.  (Lipomata  are  unaffected  in  starvation; 
attempts  to  cause  their  removal  by  starvation  have  been  un- 
successful.— Samuel.)  Death  from  starvation  takes  place  after 
the  development  of  great  muscular  weakness,  with  complete  loss 
of  power  and  deep  stupor  (Samuel).  In  the  bodies  of  animals 
dead  from  this  cause  are  to  be  noted  muscular  and  glandular 
atrophy,  passive  congestion  and  degenerative  changes,  together 
with  scanty  contents  of  the  small  intestine  and  diminished  lumen 
of  the  latter. 

Complete  inhibition  of  water  (as  in  feeding  with  material  arti- 
ficially deprived  of  its  water)  acts  quite  as  effectively  as  hunger, 
death  taking  place  in  from  eight  to  twelve  days.  Animals,  un- 
able to  quench  their  thirst,  refuse  food,  and  the  organism  is  unable 
to  adequately  supply  the  fluid  secretions  necessary  for  digestion. 
Death  probably  is  due  to  the  retention  in  the  system  of  injurious 
metabolic  products  (with  poisonous  qualities),  which  cannot  be 
flushed  out.  Actual  drinking  of  water  may  very  well  be  avoided 
by  a  number  of  animals  (rabbits,  guinea-pigs,  cats  or  parrots) 
without  injury  to  health,  provided  the  food  ingested  contain  water. 


38  Causes  of  Disease. 

Diminution  in  the  amount  of  food  ingested,  undernutrition 
(relative  or  incomplete  inanition),  is  often  met  with  in  connection 
with  diseases  of  the  alimentary  tract;  its  consequences  are  pre- 
cisely similar  to  those  of  total  withdrawal  of  food,  save  that  the 
progression  of  the  case  is  slow^er.  Usually  the  condition  is  ac- 
companied by  a  diminution  of  erythrocytes  in  the  blood  (inanition 
ancemia),  tlie  alimentary  disease  producing  wide  disturbance 
through  fluid-waste   (diarrhoea)    and  other  complications. 

Faulty  composition  of  food  causes  partial  starvation,  the  body 
suffering  loss  in  its  fat,  albumen  or  carbohydrate  should  its  nour- 
ishment lack  or  contain  but  an  insufficient  amount  of  one  of  these 
substances,  or  should  the  animal  by  preference  and  exclusively  feed 
upon  only  one  of  these  types  of  nutritive  material.  Impoverish- 
ment of  the  diet  in  such  manner  brings  about  emaciation  and 
physical  weakness.  If  lime  should  be  deficient  in  the  food  and 
water  supply  the  skeleton  will  fail  of  its  most  essential  constituent, 
that  which  gives  it  its  rigid  strength,  and  the  bones  become  soft. 

Respiratory  Faults. 

All  animals  die  by  asphyxia*  if  their  supply  of  oxygen  be 
prevented.  A  wide  range  of  factors  may  bring  about  a  diminu- 
tion in  the  proportion  of  oxygen  contained  by  the  blood,  asso- 
ciated as  a  rule  with  insufiicient  separation  of  the  carbonic  acid 
and  its  consequent  high  proportion  in  the  blood.  Primarily  this 
may  result  from  the  insufficient  access  of  atmospheric  air  to  the 
respiratory  organs,  as  by  closure  of  the  superior  orifices  \ smoth- 
ering] or  by  obstruction  of  the  respiratory  tube  [choking] 
and  constriction  of  the  latter  {strangulation,  compression  of 
the  larynx  or  trachea)  by  fluids  and  foreign  bodies  (the  latter 
also  by  lodging  in  the  pharynx  and  occluding  the  trachea),  pres- 
sure upon  the  larynx  and  trachea  by  tumors,  obstruction  by 
tumors  or  swelling  of  the  mucous  membrane  in  the  folds  of  the 
glottis  or  in  the  bronchial  tubes,  collections  of  blood,  fluid  or 
coagulated  exudates  in  the  lungs  and  bronchi, 

A  second  group  of  asphyxiating  causes  includes  interference 

♦The  editor  is  here  taking  the  liberty  of  using  the  word  asphyxia  as  the 
general  term,  including  smotherinfi  as  meaning  respiratory  obstructiun,  operative  at 
the  respiratory  orifices,  mouth  and  nose-  :  clinking,  respiratory  obstruction  operative 
within  the  mouth,  nasopharynx  or  oesophagus  (pressing  on  the  larynx  or  trachea)  ; 
strangulation,  respiratory  obstruction  by  constriction  or  pressure  from  without 
upon  the  larynx  or  throat  generally ;  suffocation,  respiratory  obstruction  by  any 
type  of  cause  operative  below  the  level  of  the  larynx,  either  within  (as  a  suf- 
focative gas)  or  without  (as  pressure  upon  the  chest).  In  English  this  meaning 
is  attached  to  asphyxia,  although  as  Prof.  Kitt  indicates  In  the  present  section 
it  really  means  pulseless;  his  own  general  terra  is  "Ersti-ckung." 


Respiratory  Disturbances.  39 

with  the  respiratory  movements,  as  in  case  of  rupture  of  the 
diaphragm,  the  principal  muscle  of  respiration,  in  case  of  its' 
immobility  or  when  it  is  forced  forward  by  flatulence,  in  case  of 
marked  pressure  from  without  upon  the  chest  walls  (animals 
standing  pressed  together  in  railway  cars),  or  in  case  of  pressure 
upon  the  lungs  by  large  fluid  collections  in  the  chest  cavities. 
Failure  of  respiratory  movement  may  also  occur  from  nervous 
origin  (pressure  upon  the  brain,,  paralysis  of  the  vagi,  spasm  of 
the  bronchial  muscles).  Premature  separation  of  the  placenta  or 
compression  of  the  umbilical  cord  in  the  maternal  canal  prevents 
ox}gen  convection  to  the  foetus. 

Furthermore,  passive  congestion  of  the  lungs,  interference 
with  the  emptying  of  the  pulmonary  veins  and  haemic  changes  in 
which  the  blood  corpuscles  have  lost  their  ability  of  taking  up 
oxygen  (carbon  monoxide  poisoning)  render  dift'usion  of  the 
gases  so  difficult  that  the  same  result  of  lowering  oxygenation 
arises,  and  the  respiratory  disturbance  eventually  advances  to  the 
stage  of  sufifocation.  The  presence  of  irrespirable  gas  and  the 
reduction  of  oxygen  in  the  air  of  an  inclosed  space  (instead  of 
20.8  per  cent.,  perhaps  only  2  to  3  per  cent.)  act  in  a  similar 
manner. 

In  one  or  other  of  such  a  variety  of  ways  asphyxia  may  be 
the  termination  of  a  number  of  diseases  and  is  the  commonest 
cause  of  death.  It  is  usually  accompanied  by  the  symptoms 
of  dyspncea  (17  Smirvoia,  from  wviw,  difficult  breathing,  shortness  of 
breathing),  labored  respiratory  movements  (sufi'ocative  dyspnoea), 
marked  increase  in  the  cardiac  movements,  spasmodic  twitching  of 
the  general  musculature  and  loss  of  consciousness.  Toward  the  close 
the  respiratory  movements  become  irregular,  sometimes  intermit 
and  suddenly  cease,  the  inspirations  occasionally  becoming  very 
deep  (terminal  respiratory  movement)  ;  and  the  spasms  weaken 
the  cardiac  action  (true  asphyxia,  actual  pulselessness,  from 
a  privitive  and  6  (7(pvy/j.6s,  the  pulse).  When  the  diminution  in 
oxygen  is  gradual  in  its  onset  these  symptoms  appear  less  promi- 
nently;  but  as  the  tissues  degenerate  from  the.  insuflicient  supply 
of  oxygen  (fatty  degeneration  of  the  heart,  liver,  kidneys)  and 
as  the  respiratory  nervous  center  loses  its  excitability,  the  patient 
dies  from  gradually  increasing  loss  of  consciousness  and  cardiac 
failure.  According  to  the  rapidity  of  onset  of  the  fatal  end  and 
the  causes  of  the  asphyxia,  the  post-mortem  findings  present  dif- 
ferent pictures.     In  addition  to  the  local  changes  due  to  strangu- 


40  Causes  of  Disease. 

lation,  obstruction  to  the  respiratory  passages  or  the  rest  of  the 
causes  mentioned,  the  most  common  features  of  this  mode  of 
death  are  found  in  the  tar-Hke,  uncoagulated,  dark  condition  of 
the  blood  (excessive  presence  of  carbonic  acid,  deficient  decarboni- 
zation)  and  in  the  presence  of  haemorrhages  in  the  hmg  and 
pleura. 

Excessive  Functional   Stimulation. 

All  organic  activity  is  accompanied  by  consumption  of  the 
essentially  functionating  material  of  the  organs  and  by  the 
formation  of  metabolic  products.  Both  of  these  factors,  especially 
the  accumulation  of  the  latter  substances  in  the  tissues  of  the 
organ,  lead  to  a  gradual  reduction  in  efficiency,  that  is,  to  fatigue. 
This  is  normally  corrected  (restoration  or  reconstitntion  of  the 
part)  during  the  intervals  of  rest,  when  the  accession  of  arterial 
blood  replaces  what  has  been  lost  and  the  lymph  current  sweeps 
out  the  waste  products  (fatigue  waste).  Should  the  various  or- 
gans be  required  to  continue  their  activity  without  intervals  of 
rest  for  a  long  time,  or  should  they  suddenly  be  overstrained, 
or  called  into  functional  effort  beyond  their  physiological  ability, 
their  parenchimatous  substance  may  be  so  affected  by  the  height- 
ened metabolism  and  so  marked  an  accumulation  take  place  of 
the  waste  products  of  fatigue  (carbon  dioxide,  phosphoric  acid, 
either  free  or  combined  as  acid  phosphates),  that  exhaustion  or 
wearing  out  results,  with  complete  abolition  of  functional  ability. 
This  condition  is  clearly  pathological  if  tissue  changes  can  de- 
velop in  the  process  and  make  the  loss  of  function  permanent 
(fatty  degeneration  or  cellular  atrophy),  or  if  the  cessation  of 
function,  momentary  though  it  be.  can  cause  in  the  vital  organs 
disturbances  involving  the  general  economy  or  the  actual  death 
of  the  individual. 

Coincidence  of  other  contributing  causes  (the  weakened  stage  in 
fevers,  traumatism  or  thrombosis)  favors  the  development  of  such 
functional  lesions  from  overexertion,  as  seen  especially  in  the 
heart,  the  general   muscles  and  in  the  nervous  system. 

General  muscular  fatigue  and  cardiac  exhaustion  mav  be 
the  cause  of  death  in  overheated  animals.  Horses  suffering  from 
thrombosis  of  the  abdominal  aorta  and  its  branches  exhibit  siens 
of  functional  disturbance  of  the  muscles  of  the  posterior  limbs, 
even  under  moderate  effort,  because  of  their  poor  arterial  supply 
and  the  accumulation  of  waste  products  from  fatigue.     The  heart 


Functional  Stimulation;   Thermal  Influences.  41 

fatigued  by  prolonged  effort  may  lose  its  power  of  contraction  to 
such  a  degree  that  it  becomes  abnormally  distended  by  the  pres- 
sure of  the  contained  blood  (cardiac  dilatation,  insufficiency  of 
the  heart),  with  ensuing  disturbance  of  the  circulation.  Over- 
stinuilation  of  the  nervous  system  by  sudden  psychical  shock  is 
not  only  in  man  productive  of  serious  results;  fright  palsy  with 
cessation  of  cardiac  action  (paraplexis)  has  also  been  observed 
in  the   lower  animals    (fowls). 

A  graduall}-  and  onl}-  moderately  increasing  demand  upon  the 
muscles  and  glands  acts  as  a  stimulus  to  their  functional  activity, 
provided  proper  nutrition  be  afforded  the  tissue,  and  results  in  func- 
tional hypertrophy,  that  is,  in  an  increased  grozvth  of  the  cellular 
elements  corresponding  to  the  demand'  for  zvork.  This  may  be 
noted  especially  in  tubular  structures  provided  with  muscular 
walls  (smooth  muscle),  where  there  is  gradually  and  spontane- 
ouslv  developed  an  increasing  competence  for  the  w^ork  required 
of  the  muscle,  as  in  the  thickening  of  the  muscular  layers  of  the 
bladder  in  case  of  gradually  narrowing  stricture  of  the  urethra 
(v.  functional  hypertrophy). 

Thermic  Influences. 

High  temperature  of  the  surrounding  atmosphere  (above  the 
body  temperature  peculiar  to  the  animal)  may  lead  to  failure  of 
heat  loss  (heat  stasis)  and  hyperthermia  of  the  entire  body  with 
fatal  termination  by  so-called  heat-stroke.  This  is  frequently  ob- 
served in  hogs  when  crowded  in  railway  cars.  The  condition  is 
most  easily  induced  if  the  dissipation  of  the  body  heat  by  evapora- 
tion is  diminished,  and  at  the  same  time  heat  production  in- 
creased in  the  animal  by  prolonged  muscular  eft'ort  or  by  rich 
feeding.  (It  is  known  from  experiments  that  warm-blooded  ani- 
mals kept  in  well-ventilated  warm  chambers  at  36  to  40°  C. 
die,  some  in  from  one  to  three  days,  others  in  from  ten  to  thirty 
days.  The  body  temperature  of  such  animals — rabbits — rises  to 
39  to  42°  C. ;  they  become  dyspnoeic  and  there  is  increase  in 
the  frequency  of  the -pulse;  the  haemoglobin  of  the  blood  is  re- 
duced, and  degenerative  changes  develop  in  the  heart,  the  liver 
and  kidneys. — Ziegler.)  The  cause  of  death  is  cardiac  failure 
(heat  rigidity)  occasioned  by  the  overheated  blood,  or  may  de- 
pend upon  a  thickening  of  the  blood  through  excessive  loss  of 
fluid  by  sweating  and   respiration    (fall  of  blood   pressure,  dimi- 


42  Causes  of  Disease. 

nution  in  vascular  tone).  As  anatomical  changes  are  found  red- 
dening of  the  skin  (in  hogs),  failure  of  blood  coagulation,  dilata- 
tion of  the  right  heart,  venous  hypersemia  of  the  lungs,  liver, 
kidneys  and  brain.  The  names  insolation  and  sunstroke  are  ap- 
plied to  that  form  of  heat-stroke  which  is  caused  by  the  influence 
of  the  direct  heat-rays  of  the  sun  upon  the  body,  particularly 
upon  the  head ;  it  is  thought  to  depend  upon  a  paralytic  dilatation 
of  the  vessels  of  the  meninges  and  cortex  of  the  brain,  and  the 
fiffection  is  accompanied  by  convulsions  and  marked  symptoms  of 
excitation    (Birch-Hirschfeld). 

The  influence  of  heat  locally  applied  occasions,  lesions  known 
as  hums  (combustio),  of  various  grades  according  to  the 
degree  of  temperature,  the  duration  of  application  and  the  resist- 
ive powers  of  the  tissues  to  heat.  Burning  may  result  from  con- 
tact with  solid,  liquid  or  gaseous  heated  matter,  or  from  direct 
action  of  a  flame  or  radiant  heat.  Short  exposure  to  a  tempera- 
ture of  40  to  50°,  or  longer  exposure  to  30  to  40°  C.  is  pro- 
ductive of  an  inflammatory  reaction  marked  merely  by  dila- 
tation of  the  capillaries  (hyperemia)  and  redness  of  the  part 
{inflammatory  hum,  erythema,  hum  of  the  first  degree  or  of  mild 
degree).  The  process  is  only  superficial,  leading  at  most  to 
desquamation  of  the  epithelium.  Exposure  to  heat  of  60  to  80° 
C.  {hum  of  the  second  or  intcmiediate  degree)  is  productive, 
in  addition  to  the  hypersemia,  of  rapid  exudation  of  serous 
fluid  from  tha  dilated  vessels  beneath  the  epithelial  layer.  The 
cells  of  the  stratum  ]\Ialpighii  are  pressed  apart  by  this,  become 
swollen,  are  loosened  from  the  papillary  bodies,  and  the  firm, 
horny  portion  of  the  epidermis  is  raised  up  to  form  a  blister. 
Through  minute  fissures,  easily  made  in  this  bleb,  pyogenic 
bacteria  may  enter,  the  fluid  contents  through  further  exuda- 
tion [leucocytes]  becoming  turbid  and  purulent.  Should  the 
blister  rupture  the  hypergemic  papillje  beneath  are  exposed,  the 
repair  of  the  epidermis  starting  from  the  epithelium  at  the  mar- 
gins of  the  lesions  or  from  remnants  of  the  ]\'Ialpighian  cells 
which  were  not  destroyed.  In  case  of  mucous  membranes,  which 
are  devoid  of  the  horny  epithelial  layer,  blister  formation  is  not 
likely  to  take  place,  the  epithelial  layer  desquamating  in  shreds ; 
and  the  denuded  surface  is  covered  by  a  coagulating  exudate,  the 
so-called  croupous  or  false  membrane.  The  more  severe  influ- 
ences of  heat,  above  80°  C.  {burns  of  the  third  degree), 
produce    searing    and    charring    {eschar    formation)  ;    the    burned 


Thcnnic  [nflnciiccs.  43 

tissue  coagulates ;  the  blood  within  the  capillaries  is  coagulated 
and  stagnant,  tlie  tissue  dying  in  consequence  and  being  trans- 
formed into  a  brownish  crust  (or  eschar).  At  the  border  of  the 
actually  involved  and  necrosed  tissue  inflammation  ensues.  Heal- 
ing follows  by  the  separation  of  the  charred  material  and  the 
formation  of  scars,  which  are  apt  to  be  of  a  radiating,  reticular 
appearance,  and  which  by  their  contraction  and  shrinkage  may 
cause  considerable  disfiguration.  All  these  degrees  of  burning 
may  coexist  as  the  heat  has  happened  to  influence  in  a  greater  or 
less  measure  one  or  more  places. 

In  extensive  burns  of  the  skin  (if  as  much  as  one-third  of 
the  body  surface  is  involved)  the  subject  is  likely  to  die.  even 
in  case  of  burns  of  no  more  than  the  first  or  second  degree. 
Death  may  take  place  within  but  a  few  hours  after  the  occurrence 
of  the  accident  with  symptoms  of  impaired  respiration,  cardiac 
weakness  and  fall  of  the  body  temperature.  In  other  cases  the 
fatal  end  may  take  place  after  the  course  of  a  week,  during  which 
there  may  have  been  apparently  favorable  progress,  pulmonary 
oedema  and  nephritis  often  developing  in  tlie  meantime.  Other 
cases  pursue  a  course  of  some  weeks'  duration  before  the  lethal 
end.  The  explanation  of  the  dangerous  features  and  fatal  termi- 
nation of  such  burns  is  to  be  sought  in  part  in  functional  dis- 
turbance of  the  skin  in  heat  dissipation,  fall  of  blood  pressure,  over- 
heating and  inspissation  of  the  blood  (cardiac  paralysis)  and  in 
part  by  the  changes  which  the  blood  corpuscles  undergo.  Dif- 
ferent investigators  (Salvioli,  ]\Iaragliano,  Castellino,  Ponfick) 
have  showm  by  experiment  and  observation  upon  human  cases, 
that  after  burns  of  the  skin  the  red  blood  corpuscles,  partly  de- 
generate (broken  into  small  particles)  and  partly  without  any 
apparent  structural  changes,  are  incapable  of  conveying  oxygen, 
and  give  up  their  hemoglobin  (partly  changed  into  methoemoglobin) 
into  the  serum,  whence  it  is  excreted  by  the  liver  and  kidneys ; 
that,  further,  the  formation  of  hyaline  thrombi  is  apt  to  take 
place  and  that  these  alterations  of  the  blood  may  be  regarded  as 
the  cause   of  death. 

Low  temperatures,  which  deprive  the  body  of  its  proper 
warmth,  may  give  rise  to  either  local  or  general  disturb- 
ances in  warm-blooded  animals.  Sensitiveness  to  the  power 
of  withstanding  cold  varies  very  much  in  the  different  animal 
species.  Fishes  chilled  to  the  freezing  point  may  seem  to  be 
lifeless,    their    lymph    frozen    into    solid    ice ;    yet    they    may   com- 


44  Causes  of  Disease. 

pletely  recover  from  such  a  condition.  Frogs  are  said  to  remain 
viable  for  hours  subjected  to  a  temperature  of  -2.5°  C,  with  the 
heart   frozen   soHd    (anabiosis). 

According  to  Koch,  resuscitation  is  possible  only  by  gradual  thawing 
and  providing  only  a  part  of  the  water  present  in  the  body  has  been 
actually  frozen ;  in  case  of  rapid  thawing,  violent  diffusion  currents  appear 
between  the  water  emerging  from  its  crystalline  form  and  the  concentrated 
albuminous  solutions  of  the  blood  and  tissues,  which  may  destroy  the 
tissues   (Koch,  Ziegler). 

Hibernating  animals  sleep  but  lightly  with  a  blood  temperature 
of  6°  C,  but  soundly  at  1.6°  C. ;  their  cardiac  beats  sink  to  eight 
to  ten  each  minute ;  breathing  is  almost  suspended,  the  movement 
of  the  lungs  caused  by  the  heart  action  alone  carrying  on  the 
feeble  gas  diffusion  in  the  lungs    (Samuel). 

The  hair  and  feathers  (especially  the  winter  pelt)  of  animals 
lessen  the  loss  of  heat  by  radiation  and  by  convection  of  the 
[warm]  air  from  the  surface  of  the  body ;  in  consequence 
of  which  animals  are  seen  to  endure  with  ease  the  ordinary  cold, 
providing  they  are  well  nourished,  move  about  freely  and  thus 
produce  heat  abundantly.  [The  loss  of  this  protective  element 
or  the  presence  in  the  hair  of  much  moisture  favoring  the  ready 
convection  of  the  heat  from  the  body  surface  reduces  tremen- 
dously the  power  of  resistance  to  cold ;  and  one  finds  the  cattle 
in  the  prairies  freezing  to  death  in  a  rain  at  a  temperature  con- 
siderably above  ice-forming  temperature,  although  were  the  hair 
dry  and  capable  of  holding  the  layer  of  warmed  air  close  to  the 
skin  the  animals  would  have  shown  no  signs  of  discomfort.] 
If  there  be  diminution  of  heat-production  because  of  insufficient 
nutrition,  and  extreme  cold,  even  well-pelted  animals  (hares  and 
deer)  and  birds  may  be  frozen  to  death.  Death  by  freezing  takes 
place  by  loss  of  sensibility  of  the  nervous  system,  with  fall  of 
body  temperature,  diminution  in  the  frequence  of  the  cardiac 
and  respiratory  movement,  cerebral  anaemia,  loss  of  muscular 
power  and  blood  coagulation. 

The  local  action  of  cold,  varying  with  duration  of  exposure 
and  intensity,  causes  tissue  changes  of  the  same  types  as  in 
burns  (frosting,  congelation).  Primarily  there  results  a  constric- 
tion of  the  vessels  of  the  part  exposed  (local  anaemia),  after 
which,  if  the  cold  continue,  the  nerves  and  muscle  tissue  of  the 
vessel  walls  become  paralyzed  and  dilatation  of  the  vessels  ensues 
with  increased  blood  content,  this  condition  usually  returning  to 


Thermic  hiftnences.  45 

normal  when  the  low  temperature  of  the  part  is  corrected.  Tem- 
peratures below  the  freezing-  point  are,  however,  likely  to  so 
disturb  the  vessel  walls  that  inllammation  of  the  tissue  (swelling 
and  redness  of  the  skin,  frostbite,  chilblain)  develops  with  or 
without  the  formation  of  blisters ;  or  after  especially  long  and 
severe  exposure  the  blood  and  lymph  circulation  cease  and  the 
tissue  dies  as  a  result.  The  necrotic  area  may  be  separated  from 
the  normal  by  inflammatory  reaction,  or  if  it  remain  moist  may 
undergo  putrefaction  through  the  influence  of  invading  bacteria. 
The  extremities  are  the  parts  of  the  body  most  commonly  sub- 
ject to  freezing,  but  it  is  seen  rather  seldom  among  animals,  for 
example,  the  scrotum  in  bulls  (Baiit:^),  the  paws  in  dogs,  in 
horses  the  thick  skin  of  the  hoof,  particularly  the  crown  and 
pastern.  Jewsejenko  and  Cadiot  have  recorded  instances  of 
necrosis  from  freezing  of  the  deeper  part  of  the  foot  in  horses 
(in  the  Russo-Turkish  and  Franco-German  wars,  as  well  as  in 
Algeria). 

By  the  term  catching  cold  (chilling)  is  meant  the  pathogenic 
action  of  heat  loss  not  sufficient  to  cause  freezing,  but  produc- 
tive of  functional  disturbances  and  inflammation  of  nerves, 
muscles,  joints  and  internal  organs.  The  laity  commonly  and 
primarily  for  almost  all  afifections  attributes  chilling  as  the  cause ; 
and  even  the  physician  often  evades  the  question  as  to  the  origin 
of  some  malady  with  the  vague  phrase  of  the  possibility  of  catch- 
ing cold,  because  of  the  obscurity  of  the  aetiology  of  the  case. 
Many  diseases  formerly  regarded  as  produced  by  exposure  to 
cold  are  now  recognized  in  the  advanced  state  of  ^etiological  in- 
vestigation as  infectious,  although  undoubtedly  there  is  a  group 
of  afifections  in  which  chilling  of  large  areas  of  the  skin  and 
mucous  membranes  may  with  confidence  be  held  responsible  as 
the  causal  agency.  Such  a  relation  is  evident  in  cases  where,  after 
unusual  exposure  to  cold  (thorough  soaking,  strong  draughts, 
falling  into  icy  water,  heat  loss  by  radiation  to  some  neighboring 
cold  object  as  a  stone  wall)  there  immediately  develop  in  the 
chilled  parts  pains,  functional  disturbances  and  symptoms  of  in- 
flammation, or  where  in  a  short  time  these  phenomena  without 
other  demonstrable  cause  appear  in  the  subjacent  or  more  distant 
parts  of  the  body.  Cats  almost  invariably  become  sick  if  they 
become  soaked  by  falling  into  the  water,  wdiile  flocks  of  sheep 
have  been  attacked  by  pleuro-pneumonia  directly  after  wool 
washing  if,  while  wet,  they  were  left  exposed  to  cold  air.     The 


46  Causes  of  Disease. 

occurrence  of  paroxysms  of  colic  (dysperistalsis)  in  sweating 
horses  after  cliilling  of  the  surface  cannot  be  denied.  Rabbits  and 
guinea  pigs  dipped  into  ice-cold  water  have  been  known  to 
quickly  sicken  and  die  from  pulmonary  and  renal  inflammatory 
affections.  As  a  further  illustration  it  is  well  known  that  the 
peritoneum  is  very  susceptible  to  the  effects  of  lowered  tempera- 
ture, and  that  in  case  of  extrusion  of  the  viscera  or  in  operations 
involving  the  exposure  of  the  peritoneal  cavity  there  often  arise, 
even  at  a  temperature  of  21°  C,  entirely  from  the  chilling  (under 
conditions  of  asepsis  and  in  the  absence  of  other  causes),  a  gen- 
eral depression  of  temperature,  attacks  of  colic,  peritonitis  and 
perhaps  a  fatal  termination. 

Hofer  has  observed  that  chilling  may  affect  even  fishes,  provided  they 
be  suddenly  changed  from  a  warm  water  to  a  cold ;  and  that  such  chilling 
causes  changes   in  the  skin    (desquamation  and  necrosis  of  the  epithelium). 

Attempts  to  frame  a  theory  explanatory  of  the  real  nature 
of  chilling  have  as  yet  been  unproductive  of  any  definite  informa- 
tion on  the  subject.  If  it  be  assumed  that  the  blood  in  the 
cutaneous  vessels  is  chilled,  it  remains  imexplained  why  practi- 
cally only  isolated  parts  of  the  body  are  affected,  although  the 
chilled  blood  flows  on  to  other  organs.  Excretion  of  blood  pig- 
ment in  the  urine  (hsemoglobinuria)  after  exposure  to  cold 
might  well  be  explained  upon  the  idea  of  chill  effects  upon  the 
blood  causing  destruction  of  the  corpuscles,  yet  in  such  cases  of 
hsemoglobinuria  there  is  usually  a  previously  developed  myositis 
and  the  red  color  of  the  urine  is  looked  upon  as  a  result  of  the 
liberation  of  muscle  pigment  and  not  as  depending  solely  on 
blood  destruction.  The  chilling  of  the  skin  causes  extensive  vas- 
cular constriction  and  the  blood  is  forced  from  the  surface  and 
accumulates  in  the  internal  or  more  deeply  lying  parts  of  the 
body.  Why  in  these  cases  the  blood  is  not  evenly  distributed 
in  the  body,  but  collects  in  special  localities,  is  an  open  question. 
Sudden  exposure  of  a  cutaneous  or  mucous  surface  to  cold  un- 
doubtedly causes  an  appreciable  vascular  tonic  contraction,  which 
may  be  ascribed  to  stimulation  of  the  vaso-motor  nerves.  This 
vascular  spasm  is  not  limited  to  the  area  directly  affected  by  the 
cold,  but  extends  consensnally  or  reflex! y  to  adjacent  or  symmetri- 
cal, or  distant  vascular  areas  (Samuel).  If,  for  example,  one  dip 
a  hand  into  very  cold  water  the  other  hand  also  becomes  paler 
(Samuel),  and  probably  everybody  has  had  the  experience  that  oc- 


Thermic  Influences.  47 

casionally  a  sudden  chilling  of  the  feet  brings  on  directly  a  reflex 
sneezing  and  nasal  catarrh.  Rossbach  has  observed  in  experiments 
upon  cats  that  by  applying  cold  compresses  over  the  abdomen  vas- 
cular constriction  passing  over  into  vascular  dilatation  develops  in 
the  mucous  membrane  of  the  respiratory  passages.  There  usu- 
ally succeeds  upon  the  vascular  constriction  a  relaxation  of  the 
vessel  walls  with  which  is  associated  a  marked  congestion  (vid. 
Hyper?emia).  Such  disturbances  are.  of  course,  commonly  cor- 
rected, the  vascular  constriction  and  internal  congestion  together 
with  the  vascular  relaxation  disappearing,  and  the  chilling  is 
realized  but  for  a  short  time  as  a  sense  of  cold  or  brief  catarrhal 
affection  by  the  subject.  \\'hy  the  same  adjustment  does  not 
occur  in  all  cases  is  not  clear.  We  only  know  as  a  fact  that  the 
chilling  leaves  in  the  skin  itself  practically  no  anatomical  altera- 
tions, that  the  sensitiveness  of  the  nerves,  contractility  of  the 
vessel  walls,  the  circulation  and  perspiration  are  entirely  re- 
stored, while  in  the  deeper  structures  the  vascular  spasm  and 
the  succeeding  vascular  dilatation  are  apt  at  times  to  be  pro- 
longed. Sometimes,  as  further  consequences,  local  engorge- 
ments, nutritive  faults  of  the  tissues,  inflammatory  exudates,  ex- 
cessive mucous  glandular  secretion  are  to  be  seen ;  sometimes 
catching  cold  may  manifest  itself  only  by  nervous  symptoms, 
functional  disturbances  and  sensations  of  i>ain  and  may  abso- 
lutely fail  to  give  any  idea  concerning  the  anatomical  changes 
of  the  tissues. 

Aft'ections  which  arise  in  consequence  of  catching  cold  are 
often  but  transient  and  are  very  apt  to  change  their  location  in 
a  system  of  tissues,  appearing  successively  at  different  points 
along  the  larger  nerves  and  in  muscular  regions  and  at  dift'erent 
joints.     For  this  reason  they  have  been  called  rheumatic  affections. 

[While  it  is  true,  as  the  author  indicates,  that  the  varied 
effects  of  chilling  of  the  cutaneous  surface  are  not  susceptible 
of  a  simple  explanation,  there  are  certain  probable  influences 
which  can  scarcely  be  overlooked.  The  development  of  congest- 
ive states  in  some  mucous  membrane  in  connection  with  the 
more  or  less  widespread  vascular  changes  beginning  in  the  skin 
may  be  held  as  oft'ering  favorable  conditions  for  the  more  active 
growth  and  penetration  of  some  microorganisms,  which  perhaps 
in  the  normal  condition,  although  present,  were  unable  to  advan- 
tageously invade  the  membrane,  and  many  of  the  catarrhs  which 
follow  refrigeration  undoubtedly  show  clear  evidence  of  such  in- 


48  Causes  of  Disease. 

fectious  agencies.  The  old  idea  that  by  causing  a  more  or  less 
prolonged  contraction  of  the  cutaneous  vessels  the  skin  secretions 
are  reduced  or  prevented  and  that  in  this  way  there  tend  to 
accumulate  metabolic  or  other  toxines  in  the  tissues  cannot  be  set 
aside.  Such  substances  have  been  thought  to  perhaps  possess 
irritant  qualities  which  disturb  the  sensory  nerves  and  muscle 
fibres  and  other  structures,  the  rheumatic  pains  and  stiffness  sup- 
posedly arising  in  consequence.  At  least  some  weight  is  to  be 
given  to  the  readiness  of  disappearance  of  such  symptoms  when 
by  warmth  and  exercise  the  general  circulation  is  stimulated  and 
skin  secretion  heightened,  these  toxines  then  perhaps  finding  more 
ready  excretion  from  the  body  than  could  be  afforded  by  the 
other  excretory  paths.] 

Electrical  Influences. 

Powerful  electrical  discharges  upon  the  animal  body  induce 
paralysis  of  the  nervous  apparatus  (especially  of  the  respiratory 
centre),  electrolytic  destruction  of  the  red  blood  cells,  local 
burns  of  the  skin  and  laceration  of  the  tissues.  Death  usuallv 
follows ;  but  the  paralysis  and  unconsciousness  may,  after  shorter 
or  longer  duration,  go  on  to  recovery.  The  larger  animals  (cat- 
tle and  horses  in  the  stall  or  in  the  open)  are  especially  liable 
to  be  struck  by  lightning  (Frohner,  Ziegenbein).  Contact  with 
live  wires  and  completion  of  the  circuit  through  the  bodies  of 
horses  occasionally  takes  place  when  they  step  upon  the  contact 
points  of  an  electric  railway  in  the  street  pavements  or  on  a 
broken  overhead  wire.'"'  Horses  have  been  killed  by  a  current 
strength  of  500  volts,  100  amperes  (Puntigam,  Mouquet,  Blanch- 
ard)  ;  alternating  currents  of  160  volts  are  sufficient  to  kill  dogs 
(Birch-Hirschfeld). 

According  to  Leblanc,  horses  are  exceptionally  susceptible  to  electricity. 
A  horse  was  killed,  for  example,  by  a  relatively  light  current  which  the 
owner  passed  through  the  bit  in  order  to  divert  the  attention  of  the  animal 
while  being  shod. 

Anatomical  changes  may  be  entirely  absent  when  death  has 
been  caused  by  electricity,  or  the  hair  may  be  found  singed  and 
the  skin  burned  by  the  electric  spark ;  and  at  the  points  of  en- 
trance and  exit  of  the  lightning  or  current,  as  well  as  in  the 
internal  organs,  the  tissues  may  be  lacerated,  with  which  lesions 

♦Birds  sit  on  telegraph  wires  witli  Impunity  because  they  are  not  in  contact 
with  the  earth. 


Electrical  and  Mechanical  Influences.  49 

haemorrhages  of  course  occur.  Along  the  entire  course  of  the 
current  tree-Hke,  branching  Hues  of  singeing  (hypersemia  and 
hremorrhages),  the  so-called  lightning  pictures,  may  be  seen  in 
the  skin  and  intestines.  In  addition  the  blood  is  dark  and  un- 
coagulated,  the  muscles  dark  brownish-red,  the  endocardium 
stained  by  the  altered  blood,  and  the  heart  muscle  at  times  the 
seat  of  hcemorrhagic  infarcts. 

Mechanical  Influences. 

Pathological  changes  are  very  frequently  produced  by  me- 
chanical force.  These  are  either  lesions  of  tissue  cohesion, 
ruptures  (breaks  in  continuity^  Icrsio  continui) ,  or  of  compression, 
as  the  constriction  of  a  hollow  organ,  condensation  of  tissues 
or  displacement  of  organs.  If  this  be  caused  by  external  forces 
or  foreign  bodies  the  process  is  spoken  of  as  traumatism  {trauma, 
rh  rpavixa,  lesiou,  lat.  IcTsio) .  The  active  agent  is  either  a  dull  (fall, 
blow,  jolt,  pressure,  pull,  friction)  or  a  pointed  or  sharp  (stab,  incis- 
ing) solid  body.  In  the  same  way  internal  mechanical  disturbances 
may  be  caused  by  adhesions  of  the  tissues,  tumors  and  other 
pathological  products  producing  constricting  influences,  or  by 
excessive  blood  pressure,  abnormal  gas  expansion  or  pressure 
by  fluids;  or  may  involve  the  functions  of  organs  (displace- 
ment of  actively  motile  stomach,  intestine,  uterus  or  muscle). 
If  the  force  gives  rise  to  loss  of  continuity  amounting  to  visible 
separation  of  the  tissue  the  lesion  is  spoken  of  as  a  zvound, 
hurt,  tear  (vidnus,  trauma  in  restricted  sense)  ;  if  affect- 
ing dense  structures  (as  bones,  cartilage  or  teeth),  as  a  break 
(fracture)  ;  if  the  tissue  be  destroyed  by  compression,  as  a  crush, 
contusion  or  bruise.  Displacements  (dislocations)  are  met  in 
joints,  bones  or  muscles,  as  zvrenching  or  luxations;  in  the  intes- 
tines as  ruptures  (hernia),  or  tzvists  (volvulus).  The  term 
stenosis  is  employed  in  connection  with  constriction  and  oblitera- 
tion of  hollow  organs ;  where  the  closure  is  caused  by  some  fac- 
tor in  the  inside  of  the  organ  it  is  spoken  of  as  an  occlusion 
stenosis;  where  it  is  due  to  external  pressure  it  is  said  to  be  a 
pressure  stenosis. 

The  results  of  mechanical  injury  are  extremely  numerous  and 
vary  with  the  size  and  character  of  the  producing  agent, 
as  well  as  of  the  local  lesion,  and  with  the  relative  importance  of 
wounded    tissue    to    the    general    organism.      A    wound    is    often 


50  Causes  of  Disease. 

complicated  by  other  factors,  as  from  the  entrance  of  microbic 
or  toxic  agencies  through  the  opening  or  breach  made  by  the 
foreign  body,  with  the  result  of  further  alteration  of  the  tissues. 
The  traumatic  agent  may  be  at  the  same  time  the  conveyor  of 
such  substances,  or  may  itself  be  a  living  parasite.  Intense 
mechanical  force  may  sometimes  without  any  evident  lesion, 
sometimes  with  manifest  lesion,  cause  serioivs  and  perhaps  fatal 
effects  upon  the  nervous  system.  For  example,  this  occurs  in  vio- 
lent concussion  of  the  body  {commotio  from  com-rnoveo) ,  espe- 
cially if  the  vertebral  column  be  directly  affected  (concussion  of 
brain  and  spinal  cord — the  former  causing  the  loss  of  conscious- 
ness, the  latter  bilateral  palsies  of  the  extremities,  the  bladder 
and  rectum).  What  the  precise  anatomical  changes  are  which 
in  such  instances  take  place  in  the  central  nervous  system  has  as 
yet  not  been  determined,  autopsy  usually  showing  nothing  that 
is   characteristic.      Possibly  the   alterations  are   molecular. 

Death  sometimes  takes  place  suddenly,  too,  from  blows  upon 
the  abdominal  wall  and  viscera.  Such  instances  are  characterized 
by  sudden  loss  of  strength,  fall  in  body  temperature,  cardiac  fail- 
ure and  diminution  of  nervous  excitability.  This  condition  is 
known  as  shock,  traumatic  stupor,  collapse,  traumatic  reflex  par- 
alysis. It  is  thought  that  the  paralysis  and  cardiac  failure  in 
such  cases  is  due  to  vagus  irritation. 

Chemical  Agents;  Poisons. 

Substances  which  harm  the  animal  body  by  their  chemical  ac- 
tion are  known  as  poisons;  the  actual  process  of  introduction  of 
the  poison  and  its  action,  as  poisoning  or  intoxication.  Probablv 
nearly  all  chemical  substances  can,  under  proper  conditions,  act 
as  poisons,  or,  in  other  words,  have  a  deleterious  influence  upon 
the  tissues ;  the  mode  and  power  of  combination  of  the  chemical 
and  the  amount  and  degree  of  concentration  in  which  it  is  present 
in  the  body  being  important  items.  For  example,  a  substance 
as  essential  for  the  bod\^  as  sodium  chloride  will  in  large  doses 
cause  vomiting  and  fatal  poisoning  in  dogs.  The  most  poisonous 
substances,  as  hydrocyanic  acid  or  nicotine,  have  absolutely  no 
eft'ect  when  given  in  the  minute  doses  of  the  homeopaths. 
Changes  in  the  relation  of  the  atoms  and  solubility  may 
transform  a  non-poisonous  substance  into  a  poisonous  one  and 
vice  versa;  of  the   two   forms   of  phosphorus,   only   the   white   is 


Chemical  Agents.  51 

poisonous,  the  amorphous  red  form  being  harmless  even  in  large 
quantities.  A  number  of  substances  which  are  insoluble  in  water, 
and  which  have  practically  no  effect  when  brought  in  contact  with 
the  skin  or  when  introduced  subcutaneously,  are  changed  by  the 
hydrochloric  acid  of  the  stomach  so  as  to  become  serious  poisons ; 
for  example,  carbonate  of  barium  is  changed  in  the  stomach 
into  the  soluble  chloride  of  barium.  On  the  other  hand,  there 
are  substances  which  are  apparently  energetic  poisons  when  in- 
troduced into  the  blood,  but  which  are  inert  in  the  stomach  be- 
cause they  are  completely  neutralized  by  the  albuminates  of  the 
gastric  juice   (Samuel). 

Many  poisons  belong  to  the  mi)ieral  kingdom  or  are  artifi- 
cially made  from  minerals,  as  arsenic,  mercury,  iodine,  bromine, 
chlorine,  lead,  copper  and  others,  and  the  various  compounds  of 
these  substances  (oxides,  sulphides,  chlorates,  chlorides,  etc.). 
The  organic  compounds,  as  alcohol,  chloroform,  hydrocyanic  acid, 
cyanide  of  potassium,  carbolic  acid  and  picric  acid,  especially 
[include  many  poisons]. 

The  vegetable  kingdom  (Samuel)  affords  many  examples  of 
poisons.  There  are  whole  families  of  plants  w'hose  genera  and 
species  possess  some  poisonous  principle  common  to  them  all.  In 
many  plants  certain  parts  may  contain  a  poisonous  substance, 
while  the  rest  may  be  quite  free  from  it  and  edible  (as  is  well 
known  in  case  of  potato  plants,  solanum  tuberosum,  w'hose  leaves, 
blossoms,  seed  and  immature  fruit  contain  the  poisonous  solanin, 
while  the  tubers  are  quite  free  from  it).  A  number  of  plants  are 
innocuous,  slightly  or  seriously  poisonous,  depending  upon  ques- 
tions of  climate,  location,  character  of  the  soil  and  cultivation ; 
the  almond  tree,  for  example,  bears  either  sweet  or  bitter  al- 
monds, according  to  the  location.  The  most  pow-erful  poisons 
contained  in  the  higher  plants  are  the  vegetable  alkaloids  (mor- 
phine, atropine,  colchicine,  digitaline,  etc.).  In  case  of  the 
lower  plants  also,  especially  the  bacteria,  there  are  products,  some 
of  which  are  marvelously  toxic,  fatal  to  large  animals  in  the 
most  minute  and  scarcely  appreciable  amounts ;  these  substances, 
analogous  to  the  alkaloids  and  enzymes,  or  of  albuminous  nature, 
are  embraced  by  the  terms  toxines,  to.ralbuuiens,  foxenaymes. 
(See  also  chapter  on  bacteria.) 

Among  animals  there  are  a  number  known  to  be  able  to 
elaborate  poisonous  secretions  within  special  glands,  especially 
the  venomous   snakes    {viper a   berus,  the   common  adder  of  Ger- 


52  Causes  of  Disease. 

many;  vipera  Redii  and  ammodytes  in  southern  Europe,  the  dif- 
ferent species  of  crotalus  (or  rattlesnake)  in  America,  possessing 
poison  glands  in  connection  with  the  teeth  or  jaws.  Scorpions, 
the  females  and  neuters  among  honey  bees,  wasps  and  bumble 
bees  possess  poison  glands  and  a  sting  at  the  posterior  end  of  the 
abdomen ;  toads  and  salamanders,  wart-like  skin  glands ;  hairy 
caterpillars,  many  biting  flies,  gnats  and  gadflies,  salivary  glands. 
There  are  certain  species  of  fish,  like  the  barbel,  whose  sexual 
glands  contain  a  poisonous  fluid  and  whose  tins  are  provided  with 
a  poisonous  substance  derived  from  the  skin  glands.  It  is  not 
certain  whether  the  occasional  poisonous  qualities  of  edible 
mussels,  oysters  and  star  fish  depend  on  transient  gland  secre- 
tions (sexual  seasons),  upon  the  food  of  these  animals,  or  whether 
they  arise  from  bacterial  changes  of  the  animal  after  death. 

The  changes  caused  by  poisons  are  partly  limited  to  certain 
localities,  partly  connected  with  general  anatomical  and  physio- 
logical changes.* 

The  poisons  may  be  arranged  for  classification  in  four  groups, 
according  to  their  modes  of  action:  (i)  Corrosive,  locally  irri- 
tative poisons;  (2)  Parenchymatous  poisons:  (3)  Hccmic  poisons; 
(4)  Nerve  and  Cardiac  poisons.  I\Iany  do  not  confine  their  in- 
fluence to  a  simple  type,  but  Excite  lesions  and  symptoms  of  mul- 
tiple character  simultaneously. 

The  corrosive  and  locally  irritative  poisons  {caustica,  irritan- 
tia)  vary  in  their  results  with  the  dosage  and  concentration  of 
application  and  with  the  character  of  the  tissue  with  which  they 
come  in  contact,  ranging  from  simple  hyperemia  and  inflammation 
to  coagulation,  eschar-formation  and  solution  of  the  tissues. 
Such  lesions  depend  upon  special  properties  of  the  substances, 
as  abstraction  of  water  from  the  tissues,  precipitation  or  solution 
of  the  albumens,  formation  of  precipitates  in  mucus  forming  tis- 
sues, solution  and  decomposition  of  urea,  conversion  of  fats  and 
carbohydrates  into  acids,  as  well  as  production  of  a  variety  of 
chemical  changes  in  the  salines  of  the  body  or  other  destruction  of 
the  structure  of  the  living  protoplasm.  Among  these  caustics  and 
irritants  (to  the  skin  or  mucous  membranes  by  direct  contact) 
are  included  the  corrosive  acids  (sulphuric,  nitric,  hydrochloric, 
oxalic,  osmic,  acetic,  carbolic,!  etc.).  the  caustic  compounds  of 
the  alkalies  and  alkaline  earths    (potassium  and  sodium  hydrox- 

•The  following  is  taken  from  the  works  of  Samuel,  Zlegler  and  Blrch- 
Hlrschfeld. 

tCarbolic   acid   or  phenol   is   really  an    alcohol. 


Chemical  Agents.  53 

ides,  quicklime,  barium  chloride),  the  corrosive  salts  of  the  heavy 
metals  (salts  of  antimony  and  mercury,  zinc  chloride,  zinc  sul- 
phate, chromate  of  potassium,  etc.),  the  poison  of  the  beetle  Lytta 
vcsicatoria,  cantharidin,  snake  venom,  the  poison  of  the  sting  glands 
of  bees,  wasps  and  hornets,  the  salivary  secretion  of  gadflies, 
stinging  flies  and  mosquitoes,  and  the  so-called  acria  or  acrid  medi- 
caments derived  from  a  number  of  plants  (croton  oil,  mezereum, 
etc.).  A  number  of  poisons,  volatile  or  gaseous  in  form,  may 
also  cause  dermal  or  mucous  membrane  irritation,  especially  to 
the  lining  of  the  respiratory  tract  during  inhalation  (irrespirable 
gases).  Should  these  irritant  and  corrosive  substances  be  ab- 
sorbed and  be  conveyed  by  the  lymph  paths  into  the  blood  and 
internal  organs,  they  may  cause,  in  addition  to  their  local  effects, 
associated  disturbances  of  the  heart  and  nervous  system,  the  liver 
and  kidneys.  Substances  inducing  degenerations  of  these  paren- 
chymatous organs  may  be  spoken  of  as  parenchymatous  poisons, 
their  effects  depending  chiefly  upon  alterations  of  tissue  meta- 
bolism, regressive  nutritive  changes  and  formation  of  precipitates 
in  the  tissues.  Among  this  group  phosphorus  belongs,  capable 
of  causing  extensive  fatty  degeneration  of  tissues,  especially  the 
liver.  Corrosive  sublimate,  chromic  acid,  cantharidin,  which  pro- 
duce marked  changes  in  the  renal  parenchyma,  are  also  irritants. 
The  production  of  argyria,  the  impregnation  of  the  tissues  with 
minute  black  particles  of  silver  after  long  continued  administration 
of  nitrate  of  silver,  may  be  thought  of  as  a  similar  process ; 
and  lead  is  an  excellent  example  of  parenchymatous  poisons, 
producing,  as  it  does,  a  wide  range  of  disturbances,  palsies,  de- 
generations and  both  local  and  general  pathological  results. 

The  so-called  hccmic  poisons  act  principally  by  depriving  the 
red  blood  corpuscles  of  their  power  to  act  as  conveyors  of  oxy- 
gen, by  inducing  their  disintegration,  liberating  and  breaking  up 
haemoglobin  or  causing  thrombosis.  Some  in  addition  may  cause 
lesions  at  the  point  of  introduction,  and  perhaps  directly  influence 
the  nervous  system.  Some  of  them  are  gases  entering  the  blood 
through  inhalation,  others  are  in  solution  and  are  derived  per- 
haps from  the  intestine  or  from  wounds.  The  best  known  blood 
poison  is  carbon  monoxide,  a  constituent  of  illuminating  gas, 
which  enters  into  combination  with  haemoglobin  to  form  carbon- 
oxyd-haemoglobin,  and  thus  prevents  absorption  of  oxygen  by  the 
blood  and  induces  a  tissue  asphyxia.  A  characteristic  feature  of 
CO  poisoning  is  the  bright,  cherry-red  color  of  the  blood.     Sul- 


54  Causes  of  Disease. 

phuretted  hydrogen  (in  poisoning  from  the  gas  of  manure  pits) 
acts  partly  by  paralyzing  the  nervous  system,  partly  by  forming 
sulphmethaemoglobin,  giving  a  greenish  (almost  cadaveric)  tint  to 
the  blood.  Hydrocyanic  acid  and  cyanide  of  potassium  also  cause 
a  rapid  paralysis  of  the  central  nervous  system,  in  addition  to 
interfering  with  oxygenation  of  the  blood  cells  and  tissues  (cyan- 
methaemoglobin,  bitter-almond  odor  in  the  organs).  Potassium 
chlorate,  nitrobenzole,  potassium  nitrate  and  amyl  nitrite  cause 
marked  destruction  of  red  corpuscles  and  transform  haemoglobin 
into  methsemoglobin,  in  which  the  oxygen  is  more  firmly  fixed 
than  in  the  oxyhgemoglobin.  The  blood,  and  of  the  organs  in  such 
instances  the  kidneys  especially,  take  on  a  striking  brown  color. 
Extensive  hsemocytolysis,  with  liberation  and  solution  of  the 
haemoglobin  in  the  blood  plasma,  giving  a  blood-red  color 
to  the  urine  (haemoglobinuria),  are  caused  by  various  toxines 
of  fungous  and  bacterial  origin  (ptallin,  helvellic  acid),  arsenu- 
retted  hydrogen,  anilin,  nitrous  acid  (fumes),  carbolic  acid  and 
other  poisons.  Coagulation  of  the  blood  and  its  sequels  are  seen 
in  poisoning  with  ricin  (from  the  seeds  of  castor  oil  plant)  and 
abrin    (from  the  seeds  of  abnis  precatorius). 

Infectious  Agencies. 

By  the  term  infection  (inficere,  to  put  into,  to  inoculate, 
to  taint)  is  meant  the  entrance  into  the  system  of  a  disease-pro- 
ducing microorganism  capable  of  self-multiplication,  a  pathogenic 
microbe. 

Nature  is  richly  supplied  with  microorganisms ;  which  on  the 
borders  between  the  animal  and  vegetable  kingdoms  represent 
primitive  forms  of  living  matter,  in  their  minuteness  are  visible 
only  with  the  aid  of  the  microscope  and  are  recognizable  as 
consisting  of  but  single  cells.  According  to  their  classification 
as  plants  or  animals,  they  are  spoken  of  as  protophytes  or  pro- 
tozoa. There  are  forms  which  are  only  visible  with  a  magnifica- 
tion of  2,000  diameters,  and  even  then  as  barely  perceptible  points 
without  definable  cellular  characters ;  and  there  are  reasons  for 
believing  that  still  smaller  organisms  exist,  invisible  with  our 
present  optical  instruments,  but  by  no  means  unreal,  being  dem- 
onstrated as  corpuscular  entities  by  other  methods,  as  by  their 
detention  in  filtration  or  by  inoculation  (so-called  invisible 
microbes). 


Infectious  Agents.  55 

Even  in  ancient  times  the  idea  prevailed  that  devastating 
epidemic  diseases  \vere  caused  by  a  Hving  contagion  (co)itagium 
vk'uni  sive  aiiimafiiiii) .  The  nature  of  these  conta^rions  re- 
maincd  hidden,  Iiowever,  to  the  physicians  of  antiquity ;  and  the 
impossibihty  of  determination  led,  especiahy  in  the  middle 
ages,  to  the  wildest  conjectures  as  to  the  nature  and  origin  of 
epidemics.  They  were  attributed  to  evil  spirits,  deemed  punish- 
ments from  on  High,  fancied  the  results  of  supermundane  pow- 
ers, of  influences  of  the  stars ;  their  origin  was  sought  in  con- 
ditions of  the  weather,  in  magnetic  and  meteorological  processes, 
in  putrid  gases  and  in  peculiarities  of  the  soil ;  and  the  hidden 
factor  was  characterized  as  a  coiistititfio  cpidcuiica  or  pcstilens. 
It  is  only  about  fifty  years  that  our  conceptions  as  to  the  real 
nature  of  epidemics  began  to  become  clearer  and  an  assured 
foundation  became  established  by  precise  observation — when,  with 
the  aid  of  the  microscope,  it  became  possible  to  demonstrate  the 
existence  of  low  vegetable  organisms  as  foreign  and  invading 
elements  in  the  diseased  body  and  to  determine  the  role  which 
they  play  in  the  production  of  disease.  In  the  last  few  decades 
this  phase  of  science,  stimulated  and  reorganized  by  the  luminous 
work  of  Louis  Pasteur  and  Robert  Koch,  improved  by  many 
technical  aids  and  demonstrative  methods,  has  fully  disclosed 
the  developmental  history  of  many  infectious  diseases.  Advances 
of  tremendous  significance  for  the  whole  of  medical  science,  dis- 
coveries and  experiences  of  the  greatest  consequence  in  the  com- 
bating and  cure  of  diseases,  have  been  attained  in  this  line  of 
study. 

The  demonstration  of  the  relation  which  a  given  microbe 
bears  to  a  given  disease  has  been  especially  facilitated  by  the 
success  of  artificial  cultivation  of  microorganisms  outside  the 
body  (in  vitro,  upon  nutritive  media)  and  of  production  at  will 
at  any  time  thereafter  of  the  infectious  disease  by  inoculation. 
Such  experiments  have  been  made  not  only  in  animals,  but  also 
in  human  beings  many  times ;  and  anyone  conversant  with  the 
subject  can  convince  himself  b}-  combined  cultural  and  inocula- 
tion experiments  that  certain  microbes  cause  certain  diseases. 
The  objection  that  the  microorganisms  are  not  the  cause  but 
the  accompaniment  or  product  of  the  disease  can  easily  be  proved 
worthless.  Of  course  there  are  microbes  in  the  body  which  have 
nothing  to  do  with  disease,  merely  surface  inhabitants  of  the 
integument    and   mucous    membranes,    able   to    penetrate    into   the 


56  Causes  of  Disease. 

blood  and  internal  organs  only  after  death  of  the  animal   (mostly 
putrefactive   organisms). 

Those  parts  of  the  human  or  animal  body  which  are  freely 
accessible  are  exposed  to  the  entrance  of  bacteria  as  of  anything 
else  from  the  exterior.  Many  of  these  microorganisms  find  fa- 
vorable conditions  for  existence  in  the  surface  of  the  skin  and 
mucous  membranes,  live  and  multiply  there  without  doing  harm, 
finding  their  nutrition  in  the  secretions  and  refuse  of  such  lo- 
calities. They  come  from  the  air  where  they  exist  in  the  dust, 
from  food  and  drink,  and,  in  fact,  from  any  objects  in  which 
they  exist  and  with  which  contact  is  had.  In  our  alimentary 
tracts  there  are  always  millions  of  bacteria*  and  other  fungi,  in 
the  stomachs  of  ruminants  countless  infusoria,  all  of  which  par- 
take of  the  nutrient  fluid  and  aid  by  certain  secretions  of  their 
own  in  the  digestion  of  the  food,  but  have  no  pathogenic  action ; 
they  are  our  table  guests  (commensualists)  and  stand  in  a  re- 
lation of  symbiosis  to  us  (living  together  for  mutual  profit). 
As  long  as  these  conditions  are  maintained  and  as  long  as  they 
obtain  their  nutrition  merely  from  the  dead  material  they  may 
be  considered  as  harmless  saprophytes  {(rairpbs,  decayed;  (pijrov, 
vegetable  growth).  Their  harmlessness  is  explicable  by  the  fact 
that  these  microorganisms  are  not  in  any  way  fitted  for  attack- 
ing the  living  substance  of  the  animal  body,  and  their  metabolism 
gives  rise  to  no  products  which  might  be  toxic  to  the  cells  and 
tissues  of  the  animal ;  or  whatever  toxines  there  may  be  are 
quickly  neutralized  by  the  body  secretions.  Besides,  their  increase 
is  held  in  check  by  the  various  adjustment  powers  of  the  body. 
The  protective  epithelium  of  the  skin  and  mucous  membranes 
prevents  their  penetration  into  the  tissues ;  they  are  expelled 
from  the  air  passages  by  the  activity  of  the  cilia  of  the  lining 
epithelium  and  from  time  to  time  by  the  expectoration  of  mucus ; 
many  are  retarded  in  their  growth  by  the  acidity  of  the  gastric 
juice  and  by  the  intestinal  secretions,  as  well  as  by  the  bile; 
large  numbers  are  expelled  with  the  excrement  from  the  in- 
testines ;  many  dry  up  upon  the  surface  of  the  body.  Moreover, 
the  various  organs  and  cells,  as  the  liver  and  phagoc3^tes  and  the 
blood  particularly,  contain  substances   of  antitoxic  and  microbici- 

•A  stained  smear  preparation  should  be  made  from  the  surface  of  the  gums, 
tongue  or  throat  of  a  convenient  cadaver  as  proof  of  the  interesting  flora  existing 
there  and  as  evidence  of  the  wandering  corpuscles  in  our  cellular  constitution.  Vld. 
for  fuller  consideration  Kitt,  Bakterienkunde  f.  Tierdrztc,  IV.  Aufl.   Wien,  1903 


Infectious  Agents.  57 

dal  power ;  and  even  thongh  they  have  gained  access  into .  the 
blood,  bacteria  may  by  these  agencies  be  rendered  harmless. 

There  must,  therefore,  be  special  conditions  afforded  before 
a  microorganism  can  become  the  actual  cause  of  infection.  In 
the  first  place  the  inicrobe  must  possess  peculiar  toxic  pozvers. 
All  microbes  carry  on  metabolic  processes  and  elaborate  a  va- 
riety of  chemical  substances  in  the  medium  in  which  they  exist. 
If  among  these  products  there  be  any  which  are  harmful  to  ani- 
mal tissue,  the  possibility  of  toxic  action  exists.  Since  Brieger 
called  attention  to  these  substances  and  indicated  their  relation  to 
disease  occurrence,  many  of  these  microbic  poisons  have  been 
proved  to  exist  by  various  investigators  and  the  process  of  infec- 
tion is  recognized  as  invariably  connnected  with  intoxication. 

In  one  class  of  microorganisms,  the  bacteria,  poisons  have 
been  demonstrated  which  are  apparently  free,  soluble  secretory 
products  of  the  bacterial  cells,  and  which  exhibit  strong  simi- 
larity to  ferments.  These  poisons  are  as  yet  not  well  defined 
from  a  chemical  standpoint;  they  are  quickly  rendered  inert  by 
being  heated  (to  50°  to  80°  C.)  and  are  peculiar  in  that  they 
do  not  manifest  their  activity  at  once,  but  require  a  certain 
period  of  incubation.  They  are,  moreover,  especially  peculiar 
in  their  specificity  and  in  the  fact  that  zvJieii  introduced  into  a 
susceptible  animal  there  is  invariably  a  speciHc  antitoxine  gener- 
ated. They  are,  therefore,  not  a  homogeneous  product  of  all 
bacteria,  but  differ  among  themselves  from  their  origin  and  the 
particular  kind  of  microbe,  each  as  a  special  product  of  a  special 
process.     These   poisons   are   collectively  called  toxines. 

According  to  Ehrlich's  theory,  a  toxine  is  a  poison  which  possesses 
two  specific  groups  of  atoms,  one  of  which,  the  Iiaptophorc,  anchors  the 
toxic  molecule  to  the  cellular  protoplasm  for  which  it  has  affinity ;  the 
second,  or  toxophorc  group,  doing  the  harm,  supplying  the  real  poisonous 
agent.  The  toxines  act  then  because  they  enter  into  chemical  combination 
with  the  cells.      (Vide    Chapter  on  immunity,  pp.   18  and  22.) 

The  proof  that  a  microorganism  secretes  a  toxine  and  through 
it  produces  disease  of  the  animal  body  is  shown  by  the  following : 
Many  bacteria  can  be  grown  artificially  upon  nutritive  culture 
media,  as  bouillon.  If  they  secrete  soluble  toxines  these  will 
accumulate  in  the  medium.  If  such  a  culture  be  passed  through 
a  filter  impervious  to  bacteria,  as  a  porcelain  filter,  the  bacteria 
will  be  retained  by  the  filter  and  the  bouillon  will  pass  through 
clear  and  quite  free  from  bacteria.     If  there  follow  the  injection 


58  Causes  of  Disease. 

of  such  a  germ-free  filtrate  (into  a  suitable  animal)  evidence  of 
toxic  action,  especially  a  specific  one,  then  we  must  be  dealing 
with  a  dissolved  toxine  yielded  by  the  bacteria.  The  best  and 
simplest  example  of  this  is  afforded  by  cultures  of  tetanus  bacilli, 
the  filtrate  from  which  produces  typical  and  characteristic  te- 
tanus symptoms,  the  dry  residue  from  the  evaporation  of  the 
filtrate  acting  in  the  same  manner. 

A  second  proof  that  the  immediate  agent  of  bacteria  is  their 
soluble  toxine  may  be  had  by  artificially  removing  the  latter  from 
the  germs.  If  water  be  allowed  to  run  for  several  hours  through 
the  residue  of  bacteria  upon  the  filter  they  will  be  washed  free 
of  the  toxines  and  can  be  inoculated  in  enormous  amounts,  by 
the  millions,  without  giving  rise  to  apparent  harm  (the  inert 
bacterial  cells  being  quickly  destroyed  by  phagocytosis  in  the  ani- 
mal body).  Yet  if  these  harmless  bacteria  be  returned  to  a  nutri- 
tive medium  where  they  can  again  multiply,  they  produce  poison 
anew,  this  collecting  in  the  substance  of  the  bacteria  and  in  the 
fluid  in  such  quantities  that  inoculation  of  even  the  smallest 
quantity,  a  very  few  of  the  bacteria,  will  produce  fatal  effects. 

The  virulence  of  toxines  is  remarkable ;  a  hundred-thousandth 
of  a  cubic  centimeter  of  the  filtrate  of  a  tetanus  culture  is  suffi- 
cent  to  kill  small  animals,  and  a  ten-thousandth  of  a  milligram 
of  the  dried  substance  will  do  the  same ;  less  than  one  milligram 
would  cause  tetanus  convulsions  in  a  human  being.  Such  facts 
prove  that  some  bacteria  are  provided  with  toxic  agencies  of 
frightfully  dangerous  power  and  explain  why,  when  such  causes 
of  disease  gain  entrance  into  the  human  or  animal  body,  they 
prove  victorious  in  their  conflict  with  the  animal  cells. 

Toxins  do  not  act  uniformly  upon  all  animals.  Intoxication  oc- 
curs only  when  they  enter  into  chemical  combination,  only  in 
bodies  whose  cells  possess  substances  (receptors)  capable  of  union 
and  having  chemical  affinity  for  the  toxine.  In  bodies  in  which 
such  receptors  do  not  exist  the  toxine  behaves  as  an  indift'erent 
substance.  This  explains  why  certain  animals  show  a  natural 
immunity  against  certain  toxines  and  why  the  bacteria  producing 
tlie  latter  are  harmless  to  these  animals,  as  chickens  are  insus- 
ceptible to  tetanus  toxine. 

There  are  some  germs  which  produce  no  toxine  separable  by 
filtration  as  a  secretion,  but  whose  toxicity  is  occasioned  by  sub- 
stances enclosed  in  the  body  of  the  microbe  and  fixed  there 
( endotoxines).     Some  of  these  substances  are  of  albuminous  na- 


Infectious  Agents.  59 

ture  {toxalhnmoi,  inycoprotciii,  bacterial  protein).  They  vary 
in  their  composition  and  modes  of  operation,  some  being  peculiar 
to  certain  kinds  of  bacteria,  others  common  to  several  forms.  In 
general  they  act  like  albumens  foreign  to  the  animal,  causing  in- 
tlammatory  changes,  necrosis  of  cells  and  tissues  and  exciting  fe- 
brile reactions.  The  dead  bodies  of  the  bacteria  act  in  the  same 
way  to  some  degree,  their  toxic  substances  being  freed  only  by 
the  death  and  maceration  of  the  microorganisms. 

A  number  of  bacteria  produce  pathological  changes  also  by 
elaboration  of  acids  and  gas-forming  substances,  as  sulphuretted 
hydrogen. 

h\  addition  to  their  chemical  action  it  should  be  said  that 
mechanical  disturbances  may  be  occasioned  by  bacteria  which,  in 
their  multiplication,  produce  masses,  perhaps  for  example  ob- 
structing the   blood  vessels. 

The  sum  total  of  the  pathogenic  properties  of  a  microbe  is 
spoken  of  as  its  virulence.  According  to  the  quality  of  toxine 
produced  and  the  energy  of  growth  of  the  microbe  in  the  animal 
body,  there  may  be  recognized  gradations  and  differences  of  in- 
tensity of  virulence  of  the  various  genera,  species,  strains  and 
individual  microbes';  their  power  of  disease  production  corres- 
sponding  with  the  same  factors.  Just  as  in  artificial  culture 
in  a  number  of  nutrient  media  a  bacterium  will  either  elabo- 
rate much  toxine  and  grow  rapidly  or  will  produce  but  little 
toxine  and  grow  slowly,  according  to  the  composition,  reaction 
and  temperature  of  the  medium ;  so  in  different  kinds  of  animals 
there  is  a  variation  in  capability  of  growth  and  toxine  production 
of  a  given  microbe.  In  adaptation  to  the  conditions  of  nutrition 
afforded  in  a  given  body  microorganisms  may  in  greater  or  less 
measure  lose  the  power  of  grovvth  exhibited  in  some  other  body, 
may  be  altered  in  their  pathogenic  power ;  this  is  spoken  of  as 
change  of  virulence  by  transmission.  Such  change  may  manifest 
itself  either  as  an  attenuation  or  as  an  intensification  of  virulence. 
The  oldest  known  example  of  attenuation  by  transmission  is  seen 
in  the  change  of  virulence  of  the  germ  of  smallpox ;  variola,  which 
in  man  is  severe  and  marked  by  pock  eruption  all  over  the  body, 
produces  in  the  cow  merely  a  local  and  mild  eruption.  In  the 
cow,  moreover,  even  in  the  first  generation,  it  is  permanently  so 
attenuated  that  after  reinoculation  in  man  it  gives  rise  to  only 
a  benign  local  eruption  (not  a  general  one).  Wide  differences 
of  virulence  exist  between  the  different   strains    [growths   of  the 


6o  Causes  of  Disease. 

same  organism  from  different  sources]  of  the  tubercle 
bacillus ;  those  obtained  by  culture  from  the  human  body  have 
become  almost  non-virulent  for  cattle  by  their  adaptation  to  man, 
although  some  strains  are  readily  transmissible.  Avian  tubercle 
bacilli  are  innocuous  for  mammals  (except  rabbits)  and  conversely 
it  is  difficult  to  infect  chickens  with  human  tuberculosis.  How- 
ever, Nocard  succeeded,  by  placing  human  tubercle  bacilli,  inclosed 
in  collodion  sacks  containing  bouillon,  in  the  peritoneal  cavity  of 
chickens,  in  so  adapting  their  growth  to  the  avian  body  that  there- 
after (in  later  generations  of  the  culture)  they  became  pathogenic 
for  birds  as  well  as  men. 

In  part,  at  least,  the  variability  in  the  virulence  of  microbes 
of  the  same  species  must  be  recognized  as  a  reason  for  the 
occurrence  of  either  a  comparatively  mild  or  a  severe  course  of 
an  infectious  disease  (formerly  called  genius  epizooticus)  as  well 
as  for  its  self-limited  termination.  For  example,  mouth  and  foot 
disease  in  some  of  the  epidemics  which  sweeps  the  country  runs 
an  unusually  severe  course  with  high  mortality,  although  under 
ordinary  circumstances  it  is  not  a  fatal  disease,  recovery  taking 
place  in  the  course  of  two  weeks.  The  investigations  of  Loeffler 
have  shown  that  the  virus  of  this  plague,  if  inoculated  from 
cow  to  cow,  gradually  loses  its  pathogenic  powers,  whereas  if 
alternately  transmitted  from  cow  to  swine  in  a  long  series  the 
virulence  is  maintained  or  even  increased.  It  is  interesting,  too, 
that  pathogenic  organisms  may  be  influenced  in  artificial  cul- 
ture outside  the  body  so  that  their  virulence  may  be  either  in- 
creased or  diminished  {change  of  virulence  by  artificial  culture 
methods).  Toussaint  and  Pasteur,  who  were  the  first  to  estab- 
lish this  possibility,  have  demonstrated  that  anthrax  bacilli, 
promptly  fatal  to  cattle,  sheep,  rabbits  and  mice,  may  be  so 
attenuated  in  virulence  by  artificial  culture  in  bouillon  at  a  tem- 
perature of  42°  C  that  they  produce  fatal  effects  only  in  mice. 
Similar  facts  have  since  been  established  in  connection  with  a 
number  of  microorganisms  capable  of  artificial  cultivation,  culmi- 
nating in  efficient  methods  of  prophylactic  inoculation   (Pasteur). 

This  is  easily  understood  when  we  realize  that  the  attenuated 
germs  give  rise  to  but  a  mild  attack  of  the  infection  when  inocu- 
lated, which,  however,  leaves  behind  an  immunity  to  the  disease. 
On  the  other  hand,  an  intensification  of  the  virulence,  even  of 
microorganisms  ordinarily  without  pathogenic  influence,  has  been 
obtained  by  other  cultural  methods,  as  in  nutrient  media  rich  in 


Infectious  Agents.  6i 

albumens  and  in  the  absence  of  oxygen  (Wiener,  Hueppe).  From 
such  considerations  it  may  easily  be  appreciated  that  virulence  is 
a  very  variable  property.* 

It  is  also  essential  for  the  development  of  an  infectious  dis- 
ease that  the  infectious  agent  should  be  afforded  a  suitable  path 
of  entrance  or  atrium  to  the  tissues.  Mere  contact  with  a  micro- 
organism does  not  necessarily  result  in  disease;  there  are  often 
pathogenic  microbes  upon  the  surface  of  the  skin  and  mucous 
membranes,  the  host  in  no  wise  suffering  in  consequence.  The 
virulent  germs  of  tetanus  and  of  spreading  gangrene  are  very  fre- 
quently present  in  the  intestinal  canal  of  herbivora  and  omnivora, 
but  without  inducing  pathological  results  as  long  as  the  mucous 
membrane  is  intact,  their  toxines  being  neutralized  and  destroyed 
by  the  digestive  juices.  So,  too,  pyogenic  and  putrefactive  micro- 
organisms are  found  in  large  numbers  in  the  intestinal  contents 
and  externally  upon  the  skin  in  healthy  human  beings  and  animals, 
becoming '  pathogenic  only  in  case  of  introduction  into  the  lymph 
and  blood  through  some  tissue  lesion. 

The  ordinary   places  through   which  microorganisms   gain   ac- 
cess to  the  tissues  are  the  external  skin  with  its  gland  pores,  the 
digestive    and    respiratory    tracts,    the    conjunctival    mucous    sur- 
faces and  the  uro-genital  passages.     The  protective  epithelium  of 
the  skin  and  mucous  membranes  interferes   with   the  penetration 
of  most  bacteria  into  the  tissues  and  with  their  toxic  action,  partly 
because  of  the  impenetrable  barrier  afforded   (the  horny  epithelial 
layer),  partly  because  the  secretions  of  normal  mucous  membranes 
may    wash    off    and     destroy    the    microorganisms     and     dilute 
their  toxines  to  such  an   extent  that  they  are   rendered   inert  or 
neutralized.     This  protective  means  is  not  an  absolute  one  against 
some  of  the  bacteria.     Some  may  directly  or  by  growth-extension 
penetrate   the   unaltered   skin   or   mucous   membranes;   or,   having 
gained    entrance   to    sebaceous    and    sweat   glands,    especially   the 
glandular    ducts    or    lymph    follicles    (which    are    open    upon    the 
surface  as  in  the  pharynx  and  intestine),  may  be  carried  into  the 
deeper    structures    by    leucocytes    (glandular   or    follicular   infec- 
tion).    Many  microbes  are  provided  with  means  of  motility  (flag- 
ella)  and  are  thus  able  to  penetrate  into  canals,  or  from  a  surface 
may  find  their  way  into  slight  depressions  or  inappreciable  defects 
in  the  epithelium,  where,  after  local  increase,  their  toxic  metabolic 

'See   further   Kitt,    Bakterienkunde   fur   Tierarzte,   M.    Perle,  publisher,  Wien, 
1903,  4th   edition. 


62  Causes  of  Disease. 

products  naturally  come  to  reach  such  a  degree  of  accumulation 
(concentration)  that  further  tissue  change  is  caused  and  opportu- 
nity thus  afforded  for  further  penetration  by  the  germs.  In  this 
manner  rats  may  be  infected  by  plague  by  merely  dropping  upon 
the  unaltered  conjunctiva  the  plague  bacteria;  and  the  trypansome 
of  dourine  (horse)  invades  the  body  by  its  own  motile  power 
through  the  mucous  membrane ;  various  bacteria,  if  they  can  gain 
entrance  into  a  duct  in  the  nipple  of  the  mammary  glands,  may 
multiply  luxuriantly  in  the  milk  and  give  origin  to  intense  sup- 
purative inflammation. 

Microbes  gain  access  to  the  digestive  tract  along  with  food 
and  drink  or  may  be  swallowed  after  being  inhaled  with  dust. 
The  special  point  of  infection  (so-called  intestinal  or  food  in- 
fection) in  this  case  is  usually  the  lymph  glands  of  the  mouth 
and  pharynx,  or  of  the  intestine ;  by  the  same  route  it  is  possible 
that  the  toxic  products  of  microorganisms,  themselves  confined  to 
the  interior  of  the  intestinal  canal,  may  be  absorbed  through  the 
blood  and  lymph  channels. 

Microbes  gain  access  to  the  respiratory  tract  by  inhalation 
(inhalation  infection)  with  dried  dust  particles  or  in  the  fine  dis- 
charge coughed  up  by  diseased  animals  and  subsequentlv  dried. 
They  are  in  this  case  in  part  retained  on  the  nasal  mucous  mem- 
brane, in  part  adhere  to  the  pharyngeal  surfaces  and  may  thence 
pass  into  the  lymph  follicles  and  extend  by  route  of  the  lymph- 
atics or  be  swallowed  (giving  rise  indirectly  to  an  alimentary 
infection),  or  they  may  be  carried  by  the  currents  of  air  into  the 
lungs  directly. 

Infection  of  the  urogenital  mucous  membrane  usually  takes 
place  by  transmission  of  the  germs  from  one  to  another  indi- 
vidual  in  the  course  of  sexual  congress    (coital  infection). 

A  most  favorable  opportunity  for  infection  is  afforded  by 
wounds  of  the  skin  or  mucous  membrane  (wound  infection), 
affording  access  to  the  microbes  into  the  lymph  spaces  and  chan- 
nels of  the  connective  tissue,  to  the  subcutaneous  and  sub- 
mucous structures,  favoring  penetration  into  the  peritoneal  cavity 
and  eventually  into  the  blood.  The  wounds  may  be  so  small  as 
to  be  inappreciable  to  the  unaided  eye,  as  some  tiny  abrasion  of 
the  epithelium ;  or  it  may  be  that  before  the  disease  actually 
appears  there  may  intervene  a  considerable  period  of  time,  the 
wound  perhaps  long  healed,  so  that  the  point  of  entrance  is  en- 
tirely   lost    (cryptogenetic    infection;    kpvwthv,    to    conceal).      This 


Infectious  Agents.  63 

latter  is  often  the  case  when  we  are  deaUng  with  a  folHcular  in- 
fection. The  various  pathogenic  microbes  do  not  possess  uni- 
form powers  of  disease  production,  of  multipHcation  and  dissemi- 
nation, granted  that  they  gain  entrance  by  one  or  other  of  the 
points  suggested.  Some  give  rise  to  infection,  no  matter  from 
what  point  they  are  introduced ;  that  is,  they  are  capable  of 
activity  from  various  atria  (tubercle  bacilli).  Others  require 
introduction  in  certain  situations  in  order  that  they  may  show 
pathogenic  efitects,  a  fixed  point  of  access.  For  example,  the  te- 
tanus bacillus,  as  already  indicated,  can  only  be  actively  patho- 
genic from  wounds ;  the  germs  of  vaginal  catarrh  and  epidemic 
abortion  naturally  (partly  effective  also  in  case  of  intra- 
vascular inoculations)  involve  only  the  genital  mucous  mem- 
branes ;  the  bacteria  of  mastitis  invade  the  lactiferous  ducts 
onh' ;    the    bacteria    of    calf    diarrhoea    confine    their    activity    to 

-  the  stomach  and   intestines.     These  peculiarities  probably   depend 
upon  the   presence   at   the   appropriate   points   of   entrance   of   es- 

*  pecially    favorable    conditions    for    multiplication    of    the    germs, 
other  parts  presenting  certain  interfering  conditions. 

Many  germs  require  some  special  underlying  condition  in 
order  that  they  may  live  and  nuiltiph'.  For  example,  the  piro- 
plasmata  must  get  into  the  blood,  because  they  can  only  obtain 
their  sustenance  under  the  conditions  aft"orded  by  the  living  blood 
and  die  out  in  the  body  fluids.  Other  organisms,  as  the  colon 
bacillus  and  vibrio  of  Metschnikoft',  thrive  best  in  the  chyme  and 
intestinal  mucous  membrane. 

Doubtless  the  condition  of  the  cells  and  juices  of  the  body 
plays  some  part  in  the  question  of  development  of  the  infection. 
The  biological  and  biochemical  differences  in  cells  and  fluids, 
designated  as  tissue  predisposition  and  tissue  immunity,  are  indi- 
cated by  the  fact  that  a  given  species  of  animal  is  by  nature  com- 
pletely resistant  to  a  certain  microbe  and  its  toxine,  surely  lethal 
for  some  other  species,  and  by  the  varying  rates  with  which  dif- 
ferent tissues  are  involved,  as  where  practically  only  one  of  the 
tissues  offers  resistance  to  the  growth  of  the  microbes  (as  the 
resistance  of  muscles  to  tuberculosis)  or  where  but  a  single  tissue 
is  involved.  Hence  the  question  of  development  of  an  infectious 
disease  depends  not  only  upon  the  existence  of  a  given  essentially 
virulent  microbe,  but  also  upon  the  defensive  powers  of  the  body, 
upon  the  antitoxic  and  microbicidal  properties  of  its  organs  and 


64  Causes  of  Disease. 

upon  the  mechanical   obstruction  to  the  penetration  of  the  germ 
into  the  tissues  (vide  pp.  18,  21). 

The  interval  between  the  entrance  of  the  microbes  into  the 
subject  and  the  manifestation  of  appreciable  symptoms  is 
spoken  of  as  the  period  of  incubation.  The  length  of  this  stage 
depends  upon  the  vital  peculiarities,  the  virulence  and  number  of 
the  microorganisms,  and  upon  the  site  of  the  infection  and  the 
predisposing  factors  in  the  animal  affected.  If  the  microbes 
are  capable  of  rapid  multiplication  and  of  generating  large 
amounts  of  toxic  material  (as  the  bacteria  of  chicken-septicaemia, 
which  rapidly  increase  in  the  circulating  blood,  or  the  colon  bac- 
teria of  mastitis  which  thrive  luxuriantly  in  the  milk  of  the 
udder)  the  period  of  incubation  is  usually  of  but  a  few  hours' 
duration.  Microorganisms  of  slow  growth,  as  tubercle  bacilli 
and  actinomycetes,  induce  functional  disturbances  only  after  the 
structural  changes  which  they  bring  about  have  attained  a  certain 
grade  of  development,  and  of  necessity  extend  their  period  of 
incubation  over  weeks  and  months.  Before  the  symptoms  are 
appreciable  clinicalh'  extensive  anatomical  changes  may  in  many 
cases  have  developed,  whence  it  follows  that  a  disease  may  be 
latent  or  occult  in  its  period  of  incubation,  although  if  the  animal 
be  slaughtered  it  is  clearly  seen  to  have  been  present  for  some 
time.  For  example,  in  the  case  of  pleuro-pneumonia  in  cattle  there 
are  often  found  characteristic  appearances  of  the  pulmonary  in- 
flammation in  animals  which  have  been  slaughtered  when  appar- 
ently quite  healthy ;  and  in  hogs  affected  with  erysipelatous  valvu- 
lar endocarditis  of  intense  grade,  the  disease  may  be  discovered 
only  on  slaughtering,  the  animals  having  shown  in  life  no 
symptoms  of  a  character  to  have  suggested  the  existence  of 
their  disease.  In  rabies  and  tetanus,  in  which  the  virus  causes 
symptoms  only  after  it  has  become  fixed  in  the  cerebral  nervous 
system  [the  toxine  in  case  of  the  latter  rather  than  the  germ 
itself],  the  disease  manifests  itself  the  more  rapidly  the  closer 
the  point  of  infection  to  the  brain ;  if  the  virus  be  inocu- 
lated  directly  into  the  brain  the  incubation  lasts  but  a  few  days, 
while  in  case  of  ordinary  subcutaneous  inoculation  it  may  be 
prolonged  to  weeks,  the  virus  being  at  first  retained  in  the  lymph 
glands.  Cases  of  infection  of  human  beings  by  the  bites  of 
rabid  dogs  manifest  rabies  in  8-14  days  where  the  wounds  are  in 
the  face,  but  when  the  hands  or  feet  have  been  bitten  the  period 
of  incubation  lasts  usually  one  or  two  months,  and  sometimes  the 


lnjcctiotis  .liiciifs.  65 

disease  does  not  appear  for  a  year.  'Jlie  inllucnce  exerted  by 
the  virulence,  the  amount  of  toxine  and  the  ])artieuhir  infec- 
tious germ  u])(in  the  period  of  infection  may  he  appreciated  after 
introduction  of  tetanus  toxine  into  mice:  the  symptoms  of  the 
disease,  depending"  upon  the  dosage,  appearing  after  varying  inter- 
vals from   12  hours  to  2 — 6  days. 

The  (lisscmiiiaUoii  and  nniltiplicafioii  of  pafluii^ciiic  i^cniis  in 
tJic  body  exhibit  a  number  of  peculiarities.  .Some  micro-organ- 
isms remain  closelv  confined  to  the  immediate  vicinity  of  the 
point  of  infection,  giving  rise  from  this  localizetl  situation  tcj  toxic 
results  in  proportion  to  their  own  disintegration  and  to  the  ab- 
straction by  the  fluids  of  the  body  of  their  toxic  substances.  Thus 
they  may  cause  lesions  only  in  the  neighboring  tissues  or  induce 
intense  general  disturbance  after  absorption.     The  tetanus  bacillus, 

ft 

for  example,  does  not  grow  free  in  the  body  (except  in  the  uter- 
ine cavity,  where,  under  anaerobic  conditions,  the  organism  can 
accumulate  in  large  quantities  after  having  once  lieen  introduced)  ; 
in  the  course  of  a  dav  or  two  after  inoculation  it  can  no  lonsrer 
be  found  at  the  site  of  infection  (wound),  nor  elsewhere  in  the 
body.  It  disappears  because  of  its  disintegration  and  through  the 
agency  of  the  phagocytes.  Its  toxine,  however,  is  absorbed  and 
causes  the  ganglion  cells  to  undergo  necrobiotic  changes.  Often 
bacteria,  as  the  pyogenic  organisms,  increase  b\  multiplication  at 
the  site  of  infection,  but  are  prevented  from  further  extension  by 
the  defensive  properties  of  the  body. 

For  the  most  part  the  germs  are  distributed  from  the  point  of 
infection  along  tlic  lymph  channels,  in  part  at  least  because  the 
newly  developed  germs  are  produced  about  the  borders  of  the  focus, 
are  swept  away  in  the  lymph  plasma  or  are  taken  up  by  the  leuco- 
cytes and  carried  elsewhere.  The  local  focus  (local  infcctio)i)  en- 
larges directly  into  the  surrounding  regions  (regional  infection)  ; 
and  the  microbes,  conveyed  by  way  of  the  lymph  channels,  are  car- 
ried deep  into  the  tissues  to  the  lymph  glands,  from  one  site  to  an- 
other, from  one  lymph  gland  to  another,  until  they  finally  reach 
the  blood.  They  ma}-  also  gain  direct  entrance  into  the  capillaries, 
veins  and  arteries  from  the  point  of  infection  (as  in  wounds  or 
ulcers,  or  by  direct  extension  by  growth  through  the  vessel  walls) 
and  be  carried  along  with  the  blood  current  (embolic  or  hcemato- 
gcnous  infection).  There  thus  are  produced  at  a  distance  from 
the  point  of  entrance  or  primary  focus  of  infection  new  deposits 
of  the  infectious  agents :  and  either  new  local   areas  of  disease,, 


66  Causes  of  Disease. 

secondary  metastatic  foci  of  infection,  are  caused,  or  the  micro- 
organisms are  widely  disseminated  throughout  the  whole  body 
{general  infection,  hactericcmia).  As  an  illustration,  streptococci  of 
epidemic  coryza  in  the  horse  gain  access  to  the  pharynx  with  the 
drinking  water  or  with  the  inspired  air ;  they  here  first  give  rise  to 
a  purulent  catarrhal  inflammation,  penetrate  by  direct  growth  into 
the  pharyngeal  follicles,  gradually  make  their  way  along  the 
Eustachian  tubes  to  the  middle  ear  and  here  set  up  a  similar  puru- 
lent inflammation.  Being  carried  away  by  the  lymph  current  and 
by  leucocytes,  they  give  rise  to  abscess  formation  in  the  retro- 
pharyngeal lymph  glands,  and  by  going  lower,  in  the  cervical  nodes  ; 
and,  too,  they  may  be  swallowed  and  infect  the  mesenteric  lymph 
glands  as  they  pass  along  the  chyliferous  tract.  Passing  from,  the 
lymph  glands  to  finally  reach  the  blood,  they  are  disseminated  by 
the  latter  generally  throughout  the  body,  and  cause  a  variable  num- 
ber of  metastatic  abscesses  in  such  situations  as  the  brain,  lungs, 
liver  and  kidneys,  eventually  a  septico-pysemia.  In  similar  way 
infection  of  the  umbilical  vein  in  the  new-born  by  pyogenic  bacteria 
causes  primarily  a  local  abscess-formation  at  the  umbilicus,  fol- 
lowed by  multiple  venous-embolic  abscesses  in  the  liver,  later  in  the 
lungs,  the  joints  and  elsewhere. 

It  may  happen  that  at  the  point  of  infection  the  local  lesions 
are  so  slight  as  to  be  appreciable  only  by  microscopic  study,  that 
the  microbe  passing  from  this  point  first  lodges  in  the  lymph 
glands  or  may  perhaps  even  pass  through  several  lymph-nodes 
without  occasioning  any  disturbances,  multiplying  and  manifesting 
its  influences  only  after-  it  has  gained  access  to  the  blood  and 
circulated  in  the  body  and  become  fixed  in  this  or  that  position 
at  a  distance  from  the  original  site  of  entrance.  The  tubercle 
bacillus,  for  example,  may  be  absorbed  from  the  intestines  with- 
out causing  any  alterations  in  them,  but  giving  rise  to  caseation 
of  the  mesenteric  lymph-nodes ;  or  these  may  be  traversed  by  it, 
the  germ  gaining  access  to  the  blood,  and  perhaps  first  deposited 
in  the  bone-marrow,  where  it  gives  origin  to  the  primary  tubercu- 
lous focus. 

The  physiological  movements  and  changes  of  position  of  the 
intestines  and  muscles  aid  in  great  measure  the  spread  and  dis- 
tribution of  the  invading  and  multiplying  microorganisms : 
pyogenic  microbes  which  have  gained  access  to  the  peritoneal 
cavity  are  apt  to  be  spread  over  the  whole  peritoneal  sur- 
face by  the  peristaltic  movement  of  the  intestine,  the  resulting  peri- 


Infectious  Agents.  6y 

tonitis  as  a  consequence  being-  generally  a  dilluse  one.  Tuber- 
cle bacilli  having  effected  an  entrance  into  the  pleural  or  peri- 
cardial cavities  multiply  in  the  lymph  and  are  actually  rubbed 
into  the  whole  serous  surface  by  the  movements  of  the  heart  and 
lungs.  For  this  reason  there  usually  occurs  in  these  regions  a 
disseminated,  dense  eruption  of  tubercles  involving  the  whole 
pleura,  pericardium  and  epicardium.  So,  too,  currents  in  the 
secretory  fluids  on  mucous  surfaces  are  favorable  to  the  dissemina- 
tion of  microorganisms ;  and  the  covering  of  these  surfaces  permits 
migration  and  generalization,  especially  of  the  motile  forms. 
Tubercle  bacilli  may  thus  reach  the  larynx  in  the  bronchial  secre- 
tions from  cavities  in  the  lungs,  and  if  retained  may  occasion 
laryngeal  ulceration ;  pyogenic  bacteria  from  the  pharynx  may  pass 
to  the  Eustachian  tubes  and  middle  ear  in  horses ;  and  in  case  of 
infection  of  the  milk  ducts  of  the  nipple  the  dift'erent  kinds  of  bac- 
teria in  the  milk  and  milk  passages  advance  into  the  parenchyma 
of  the  udder  and  give  rise  to  mastitis. 

The  pathogenic  action  of  bacteria  is,  as  already  indicated,  for 
the  most  part  a  toxic  process,  but  also  in  some  degree  a  mechan- 
ical one;  it  is  governed  both  by  the  properties  and  the  quantity 
of  the  e.vfrcniely  varied  metabolic  products  elaborated  by  the 
individual  microbes,  but  is  also  dependent  upon  factors  deter- 
mined by  the  place  of  infection  and  by  the  predisposition  of  the 
tissues.  Local  and  general  eft'ects  are  distinguishable ;  first  by  the 
fact  that  at  the  original  point  of  infection  and  at  metastatic  locali- 
ties anatomical  lesions  are  originated  (inflammations,  degenera- 
tions, necroses,  proliferations,  depending  upon  the  nature  of  the 
microbe,  both  in  the  sense  of  a  mere  foreign  body  and  of  the  pecu- 
liarity of  its  constituent  materials)  ;  and,  second,  by  the  develop- 
ment of  general  metabolic  disturbances,  especially  fever,  from  the 
generalization  of  the  infectious  agents  and  their  products.  In 
each  case  the  phenomena  are  expressions  of  tissue  reaction  to  the 
noxious  foreign  microbe  undergoing  multiplication  from  time  to 
time  in  the  system  (v.  chapters  on  fever,  limiting  inflammation). 
Each  kind  of  pathogenic  microorganism  manifests  a  fixed  mode 
of  action,  determined  by  its  manner  of  multiplication  in  the  tis- 
sues and  the  particular  nature  of  its  toxic  product  (specific 
action),  and  therefore  produces  a  specific  disease.  In  case  of 
other  causes  of  disease  there  is  no  uniformity  of  action,  but,  on 
the  contrary,  a  variability ;  or,  better,  it  may  be  said  that  other 
or  non-infectious  diseases  mav  occur  in  the  same  form  from  the 


68  Causes  of  Disease. 

effect  of  a  variet\  of  agencies.  A  nasal  catarrh  may  be  caused 
by  the  inhalation  of  (hist,  irritant  gases,  chemical  llnids,  the 
influence  of  cold  upon  the  external  surface  of  the  body,  or  from 
infection:  cold  may  produce  in  one  subject  painful  peristalsis 
(colic),  in  another  muscular  rheumatism,  in  a  third  a  coryza,  a 
pneumonia,  an  intestinal  catarrh.  In  infectious  diseases  the  body 
generally  reacts  with  uniformity  in  a  definite  manner ;  the  basic 
symptoms  and  lesions  are  invariably  manifest,  and  it  is  possible 
to  decide  from  the  presence  of  certain  signs  of  the  disease  that  a 
definite  type  of  infection  exists.  By  specificity,  therefore,  we 
understand  that  each  infectious  disease  is  the  result  of  fixed  in- 
fectious agents  and  not  of  anything  else.  Anthrax  is  always 
caused  by  the  anthrax  bacillus,  and  never  by  any  other  microbe 
or  noxious  agency  of  any  sort ;  glanders  is  caused  by  the  glanders 
bacillus ;  smallpox  by  the  smallpox  contagium.  There  are,  how^- 
ever,  some  micro-organisms  which,  because  of  similarity  of  toxic 
properties  and  analogous  modes  of  multiplication,  give  rise  to  the 
same  anatomical  tissue  changes,  so  that  clinically  the  same 
anatomical  types  of  disease  are  produced  by  several  kinds  of 
germs  (the  groups  of  the  pyogenic  bacteria,  the  micro-organisms 
of  septicaemia,  of  moist  gangrene  and  of  mastitis).  Such  in- 
fectious diseases  are  said  to  be  polybacterial. 

Variations  in  flic  duration  of  infectious  discuses,  modifications 
and  degrees  of  anatomical  changes,  ore  proportioned  in  the  sei'cr- 
ity  of  the  infection  to  the  grade  of  virulence  of  the  microbes, 
and  are  dependent  as  well  upon  the  place  of  entrance  of  the  infec- 
tion and  the  predisposition  of  the  tissues.  Just  as  a  corrosive 
substance,  an  acid,  depending  upon  whether  it  comes  in  contact 
with  animal  tissue  in  concentrated  or  dilute  form,  produces  either 
an  eschar,  tissue  necrosis,  inflammation  or  mere  hyperaemia.  so  a 
difference  is  appreciable  in  the  action  of  microbes  according  as 
they  are  highly  toxic  or  more  or  less  attenuated.  The  importance 
of  the  factor  exerted  by  the  place  of  entrance  of  the  infection  is 
indicated  by  the  studies  of  Arloing,  Cornevin  and  Thomas  upon 
the  bacillus  of  symptomatic  anthrax  ("black  leg")  ;  this  micro- 
organism, if  inoculated  into  the  muscles  and  subcutaneously.  kills 
animals  after  intense  symptoms ;  but  if  the  inoculation  be  made 
into  the  trachea  or  intravenously  there  follows  merely  an  abortive 
course,  which,  however,  is  succeeded  by  an  immunity.  \'ariations  of 
susceptibility  and  resistive  powers  in  different  animal  species  and 
individuals    to    precisely    the    same  infectious    agent    may    cause 


Jiifcctioiis  .li^ciits.  69 

marked  variations  in  the  clinical  and  anatomical  picture  of 
the  same  infectious  disease.  I'hus  a  certain  strain  of  glanders 
bacilli  has  been  known  to  cause  in  a  horse  a  chronic  glanders 
lasting  over  several  years,  but  in  guinea-pigs  and  field  mice  a 
very  acute  type  of  the  disease;  the  bacillus  of  hog-erysipelas,  pro- 
ducing in  one  hog  an  acute  septicaemia,  to  cause  in  a  second  a 
slight  urticaria,  in  a  third  a  chronic  cardiac  valvular  affection. 
The  influence  of  tissue  resistance  upon  the  disease  picture  is 
especially  apparent  when  inoculations  of  the  organisms  of  chicken- 
cholera  of  high  grade  of  virulence  are  made  into  rabbits  previously 
treated  by  serum  injection.  Rabbits  which  have  not  been  previ- 
ously subjected  to  serum  injection  succumb  to  hypodermic  inocu- 
lation of  but  a  small  number  of  bacteria  as  early  as  from  12  to  24 
hours,  dying  of  severe  acute  septicaemia ;  those  previously  injected 
and  then  subjected  to  the  same  inoculation  die  only  after  5  to  14 
days,  and  then  show  extensive  purulent  phlegmons,  purulent  and 
fibrinous  pleurisy  and  pericarditis,  or  merely  an  ansemia  as  a  re- 
sult of  the  prolonged  infection. 

Recovery  from  an   infectious  disease  usually  leaves  thereafter 
a  certain  degree  of  ininiunity   (v.  active  immunity,  p.  2/). 

Sometimes  several  kinds  of  pathogenic  organisms  gain  en- 
trance at  the  same  time  through  one  point  of  infection,  the  result- 
ant infection  being  thus  a  complicated  one  (mixed  infection)  ;  or 
after  the  individual  is  attacked  by  one  infection  other  types  may 
invade  (secondary  mixed  infection).  The  former  condition  is 
seen  when  the  infective  matter  from  the  beginning  contained  sev- 
eral varieties  of  pathogenic  germs,  as  where  a  wound  is  contami- 
nated with  earth  containing  both  spores  of  tetanus  bacilli  and  pus 
bacteria,  or  where  a  cow's  nipple  is  soiled  with  filth  and  dung 
m  which  there  are  streptococci  and  colon  bacilli.  So,  too,  micro- 
organisms which  have  existed  indefinitely  upon  the  surface  of 
some  mucous  membrane  may,  if  occasion  presents,  penetrate  into 
the  tissues  along  with  some  other  type  of  infection  and  combine  with 
the  latter  in  producing  pathogenic  effects  ;  thus,  should  there  be  pro- 
duced by  some  foreign  body  an  injury  to  the  tongue  or  pharynx 
of  the  cow,  the  various  putrefactive  organisms  living  as  sapro- 
phytes in  the  mouth  may  occasion  with  pyogenic  bacteria  a  mixed 
infection.  The  second  form  of  mixed  infection,  the  successive 
invasion  of  a  second  or  third  pathogenic  germ,  may  be  noted 
where  local  changes  'from  a  primary  infection  bring  about  condi- 
tions which  facilitate  the  access  and  growth  of  other  microbes;  as 


70  Causes  of  Disease. 

when  ulceration  has  occurred  in  the  primary  infection  and  the 
protective  epitheHum  has  been  lost,  or  when  in  the  course  of  a 
disease  the  bactericidal  substances  normally  present  in  the  fluids 
of  the  body  have  been  exhausted  and  the  resistance  of  the  tissues 
reduced  in  consequence.  Not  infrequently  such  mixed  infection  is 
to  be  seen  in  hog-cholera,  the  micro-organisms  of  which  cause 
necrotic  and  coagulative  destructive  changes  in  the  intestinal 
mucous  membrane  and  general  wasting;  there  is  thus  prepared  so 
suitable  a  culture  medium  for  the  sputum  bacteria  and  necrosing 
bacilli  present  in  the  pharyngeal  mucus  and  in  the  intestinal  con- 
tents that  these  readily  penetrate  into  the  tissues  and  materially 
contribute  to  intensify  the  disease  and  hasten  a  fatal  termination. 
Admixture  with  or  contamination  (association)  of  an  infection  by 
one  or  more  other  types  of  pathogenic  microbes,  each  with  its 
special  properties,  and  the  combined  action  of  all,  as  a  rule  causes  a 
severe  course  of  the  infectious  disease  and  occasions  unusual 
pathological  processes   {compUcations). 

The  mere  presence  and  microscopic  recognition  of  several  types  of 
microbes  in  any  focus  of  disease  or  in  the  tissues  of  the  cadaver  by  no 
means  warrant,  without  other  knowledge,  the  assumption  that  there  has 
existed  a  mixed  infection ;  after  the  death  of  the  animal  great  numbers 
of  saprophytic  organisms  living  on  the  surface  of  the  mucous  membranes 
wander  into  the  organs,  and  necrotic  or  ulcerating  foci  in  the  lungs,  intestine 
or  skin  are  apt  to  harbor  the  same  sort  of  organisms  from  the  air  or  food 
(so-called  symbiotic  bacteria).  The  association  of  such  essentially  non- 
pathogenic germs,  or,  too,  of  pathogenic  microbes  with  another  pathogenic 
variety,  may  (as  especially  pointed  by  Leclainche-Vallee  in  studies  on 
symptomatic  anthrax)  determine  actual  infection ;  for  example,  a  symbiotic 
bacterium  may  prevent  phagocytosis  by  a  negative  chemotactic  power  and 
thus  produce  conditions  favoring  the  increase  of  the  other  infecting  agent. 
This  should  not  be  interpreted  as  meaning  that  a  given  microorganism 
cannot  alone  cause  its  special  disease,  and  that  only  when  in  association 
with  other  microbes  can  produce  its  effect ;  it  merely  applies  to  special 
conditions  in  which  the  specific  infectious  agent  is  attenuated  or  is  situated 
in  an  unsuitable  point  for  infection.  All  known  pathogenic  microorganisms 
are  individually  capable  of  giving  origin  to  their  peculiar  infections,  and 
each   is  the   specific  bearer   of   such   infection. 

Those  micro-organisms  regarded  as  pathogenic  may  be  classed 
in  two  groups :  In  the  first  group  are  microbes  usually  living  in 
the  external  world,  but  inducing  disease  in  the  animal  body  if  by 
accident  they  gain  access  to  it  (ectoge)ious  infectious  agents, 
facultative  parasitic  microbes).  The  diseases  arising  from  this 
group  affect  individual  animals  here  and  there,  or  may  attack  a 


Infectious  Agents.  71 

number,  provided  there  be  opportunity  of  convection  from  their 
habitat  in  the  soil  to  the  animal  body  with  water,  food,  etc.  They 
are  essentially  of  telluric  origin,  and  it  is  customary  to  speak  of 
spontaneous  disease  or  miasmatic  {t6  /jLiaafia,  from  fxiaivu,  to  con- 
taminate) origin  in  this  connection.  In  the  second  group  are 
included  microorganisms  which,  being  exclusively  adapted  to  the 
animal  body  from  an  indefinite  period,  live  and  thrive  in  it  as 
their  habitat  (entogeuous  infectious  agents,  obligate  parasitic 
microbes).  Diseases  occasioned  by  these  do  not  appear  as  spon- 
taneous infections,  but  occur  only  when  a  human  being  or  animal 
comes  in  contact  with  a  previously  infected  individual  or  with 
desquamated  or  excretory  material  from  such  an  individual  in 
such  manner  that  the  infectious  agent  can  pass  to  the  former. 
Such  instances  are  spoken  of  as  contagious  i)i  feet  ions  diseases. 
[Among  many  there  is  to-day  a  strong  tendency  to  deny  the 
existence  of  pure  miasmatic  infections,  and  thus  to  regard  the 
terms  contagious  and  infectious  as  synonymous,  such  persons  hold- 
ing that  the  so-called  miasmatic  diseases  are  caused  by  organisms 
which  are  essentially  facultative  parasites,  und  in  more  or  less 
direct  manner  have  come  from  previously  diseased  individuals. 
The  difiference  of  view  is  by  no  means  a  vital  one,  and  the 
author's  recognition  of  their  immediate  derivation  from  a  source 
other  than  a  previously  diseased  individual  is  correct.  In  the 
sense  that  these  facultative  parasitic  microbes  once  afifecting  an 
individual  may  be  further  transmitted,  his  division,  however,  be- 
comes unnecessary,  since  in  this  manner  all  infectious  diseases  are 
contagious.] 

A  certain  number  of  infectious  maladies  may  be  acquired  in 
both  ways  ;  originating  primarily  from  the  soil,  the  microorgan- 
isms multiply  in  the  animal  body  and  then  are  transmitted  from 
the   diseased   to   other   individuals    (contagio-miasmatic   diseases). 

The  fact  that  some  microorganisms  thrive  only  in  the  animal 
body  and  die  when  in  the  external  world  is  a  phenomenon  of 
adaptation.  It  may  be  assumed  that  all  these  obligate  parasitic 
germs  originally  lived  a  free  saprophytic  life  in  nature,  but  having 
accidentally  gained  access  to  an  animal  body  thrived  therein  and 
by  rapid  succession  of  generations  usual  to  such  low  organisms 
acquired  a  special  adaptation  for  the  conditions  thus  afforded  and 
lost  their  faculty  of  propagation  outside. 

Changes  in  nutritional  conditions  are  likely  to  cause  changes 
in  their  metabolism,  and  the  influence  which  invading  microbes  have 


72  Causes  of  Disease. 

upon  the  tissues  of  the  body  depends  in  part  upon  their  metaboUc 
activity  and  metabohc  products.  From  investigations  of  Wiener 
it  has  been  shown  conclusively  that  a  type  of  bacteria  common  to 
the  human  intestine  and  regarded  as  entirely  harmless  in  this 
situation  and  in  the  excreta,  can  by  special  nutritive  influence  be 
so  transformed  as  to  acquire  highly  toxic  properties  (the  so-called 
eolon  bacilli,  living  as  saprophytes  in  the  colon).  If  fed  ordina- 
rily to  rats  they  give  rise  as  a  rule  to  no  disturbances  whatever, 
but  if  the  colon  bacilli  have  been  cultivated  for  a  few  days  under 
anaerobic  conditions  on  a  medium  specially  rich  in  albumen  (eggs) 
they  acquire  an  intense  virulence,  and  if  fed  to  rats  produce  a 
severe  ami  almost  invariably  fatal  enteritis.  Although  such 
transformation  of  a  non-toxic  saprophyte  into  a  toxic  pathogen 
cannot  ofif-hand  be  accomplished  with  other  micro-organisms,  this 
isolated  fact  proves  that  it  is  possible  for  infections  of  a  character 
new  and  imknown  to  us  to  arise  from  time  to  time ;  and  as  a 
matter  of  fact  spontaneous  infectious  diseases  do  now  and  again 
appear  which  have  not  been  previoi:sly  observed  and  which  are 
to  be  regarded  as  rarities.  It  is  a  pure  accident  when  the  special 
germs  are  brought  into  contact  with  the  human  and  animal  body ; 
and  it  is  further  conditional  upon  special  circumstances  of  nutri- 
tion whether  the  microbe  possess  virulent  properties,  as  in  case 
of  the  meat  intoxications  caused  by  various  microorganisms, 
sausage  poisoning,  diarrhoea  and  vomiting  and  wound  infections. 
Some  infectious  diseases  are  of  very  frequent  occurrence  because 
the  agent  is  widel}-  disseminated  in  nature  or  because  opportunities 
for  transmission  to  the  animal  body  are  often  afforded.  For  in- 
stance, the  tetanus  bacillus  exists  in  the  soil  in  many  localities, 
and  wounds  are  often  contaminated  by  dirt,  the  opportunitv  for 
tetanus  infection  being  correspondingly  common.  Such  wide- 
spread microorganisms  and  their  infectious  diseases  are  spoken 
of  as  ubiquitous.  As  the  alpine  rose  and  reindeer  moss,  palms 
and  cacti  flourish  only  within  certain  geographical  limits,  and  as 
poisonous  snakes  and  the  different  kinds  of  insects  have  their 
habitats  only  in  certain  parts  of  the  earth ;  so  certain  microbes 
occur  only  in  certain  lands,  where  alone,  too,  the  corresponding 
infectious  diseases  arise  as  spontaneous  affections.  Such  districts 
are  foci  in  which  annually  a  certain  number  of  cases  are  likely 
to  occur,  and  it  is  said  that  the  disease  is  established  in  such 
places  {indigenous,  cudeuiic).  Truly  contagious  diseases  ma}- 
also  be  endemic,  provided  in  a  certain  district   (irrespective  of  soil 


Infections  Agents.  73 

conditions)  there  are  al\va\s  a  number  of  animals  suffering  from 
the  special  infectious  disease,  so  that  others  from  these  may  in 
turn  acquire  the  affection.  When  an  infectious  disease  occurs  in 
isolated  cases  here  and  there  it  is  spoken  of  as  a  sporadic  disease ; 
if  many  or  great  numbers  of  individuals  are  affected,  it  is  spoken 
of  as  a  plague,  an  epizootic  {epidemic)  ;  if  it  extend  over  large 
areas,  'and  if  not  merely  one  species,  but  many,  are  aft'ected,  it  is 
called  a  panzootic  {pandemic).  Animal  diseases  transmissible  to 
man  may  be  spoken  of  as  androzoonoses. 

The  separation  of  spontaneous  from  contagious  infections,  the 
recognition  whether  a  microbe  is  miasmatic  or  purely  contagious, 
is  of  importance  in  dealing  with  epidemic  diseases ;  the  purely 
contagious  diseases  can  be  eradicated  by  measures  protecting  the 
well  from  the  diseased  animals  and  their  excrementitious  matters. 
This  has  been  demonstrated  in  the  extirpation  of  cattle  plague, 
pleuro-pneumonia  and  hydrophobia  from  districts  in  which  for- 
merly they  were  rife. 

SU^niARY   OF    THE    AIOST    IMPORTANT    INFECTIOUS 
DISEASES  AND  THEIR  AGENTS.* 

I.       Bacteriaemias,    Septicaemias. 

Bacillus  az'iscpticus  [Boct.  az'iscpticuin  s.  az'icidufu  ) ,  septic:emia 
of  birds  and  rabbits   (chicken  cholera). 

Bac.  pleuriscpticus,  sporadic  and  epidemic  septicaemia  of  all 
domestic  animals  (bac.  hoznscpticus,  suiscpticus) ,  deer  and  cattle 
plagues,  pastcurcUosis  hovis. 

Bac.    antJiracis,   anthrax   of   domestic   animals   and   man. 

Bac.  a\icn:atis  nialigi:i,  spreading  gangrene  of  domestic  ani- 
mals and  man. 

Bac.  sarcoplixscuiafos  boz'is.  symptomatic  anthrax  of  cattle. 

Bac.  gastroinycosis  czis,  bradsot  of  sheep.  [Bradsot  is  a  dis- 
ease of  sheep  in  northern  Europe,  by  man\'  regarded  as  a  form 
of  symptomatic  anthrax.] 

Bac.   pcstis  iarandi,   reindeer  plague. 

Bac.  rhusiopathicc  suis,  swine  erysipelas. 

Bac.  suipesfifer,  hog  cholera. 

Bac.  pcstis  buboniccr,  human  bubonic  ])lague,  transmissible  to 
swine  and  rats. 


*For   detailed   description   and    technique   of    investigations,    v.    Kitt,    Bakterien- 
kunde  f.   Ticrdrxtc,  IV.  Aufl.,   Wien,   lOUo. 


74  Causes  of  Disease. 

II.     Toxic  Infections. 

Bacillus  t  eta  III,  tetanus  in  all  animals  and  man. 
Bac.  hotulinus,  sausage  poisoning  in  man. 
Bac.  enteritidis,  meat  poisoning  in  man. 
Bae.   dysenteries  zitulorum,  diarrhoea  in  calves. 
Vibrio    Metschnikovi,    vibrio   cholera    of   chickens    [microspira 
Metschnikovi,  irregular] . 

III.     Inflammatory    and    Pyogenic    Organisms. 

Staphylococcus  pyogenes  aureus  (albus,  f!a-rus,  citreus),  sup- 
puration of  wounds,  furunculosis. 

Streptococcus  phlogogenes  sive  pyogenes  (various  forms), 
suppuration  of  wounds. 

Micrococcus  tetragenns,  umbilical  suppuration  in  calves. 

Bacillus  mallei,  glanders  in  horses  and  man. 

Bac.  lymphangitidis  ulcerosa;,  lymphangitis  in  horses. 

Saccharomyccs  farciminosus.   furunculosis   in  horses. 

Strcptothrix  farcini  boiis,  furunculosis  in  cattle  [Nocard's 
pseudotuberculous  nodules  in  the  skin  and  viscera  of  cattle]. 

Streptococcus  equi,  contagious  coryza  of  the  horse. 

Bacillus  acncos  cqiii,  contagious  pustular  dermatitis   of  horse. 

Bacterium  phlegniasice  ubcris  (a  number  of  varieties),  mastitis 
in  the  cow. 

Streptococcus  mastitidis  (a  number  of  varieties),  mastitis  in 
cow. 

Micrococcus  mastitidis  gangramoscc  oris,  mastitis  of  sheep. 

Bacillus  py clone phritidis  boris,  nephritis  of  cow. 

Bac.  pyocyaneus,  purulent  inflammations. 

Bac.  coli  connniiiiis  (a  number  of  varieties),  various  forms  of 
cellulitis,   mastitis,   nephritis   and  enteritis. 

Botryomyccs  ascofornians,  suppuration  and  granuloma  forma- 
tion in  horse. 

Cladothrix  canis,  various  suppurations  in  the  dog. 

IV.     Diphtheritic  Necroses. 

Bacillus  nccropJiorus,  traumatic  necrosis,  multiple  coagulation 
necrosis  of  mucous  membranes,  liver  and  lungs  in  cow,  horse  and 
sheep. 

Bac.  diphthericc  colunibarum,  pigeon  diphtheria. 


Infectious  Agents.  75 

Bac.    diphtheria   avium,   chicken   diphtheria. 
Bac.    diphthcricc   Jioiniiiis,   (hplitheria    in   man,   exceptionally   in 
cats  and  birds. 

V.     Tuberculosis  and  Actinomycosis. 

Bacillus  tuberculosis,  tuberculosis  of  man  and  the  lower  ani- 
mals   (varieties  in  birds  and   cold-blooded   animals). 

Bac.  bronchiolitidis  vituli,  cheesy  pseudotuberculosis  of  the 
lungs  in  the  cow. 

Bac.  pseudotuberculosis  oz'is,  in  sheep. 

Actinomyces  bozis,  actinomycosis  of  cow   (with  varieties). 

Streptothrix  caprce,  pseudotuberculosis  of  the  goat. 

VI.     Specific  Diseases  of  the  Sexual  Organs. 

Bacillus  abort ivus  z'accaruui,  epidemic  abortion  of  cows. 
Micrococcus  abortivus  equi,  epidemic  abortion  of  mares. 
Streptococcus  zaginalis  vaccariim,  contagious  vaginitis  of  cows. 
(Trypanosoma  eqniperduni  s.  tJagelose),  dourine  in  horse. 
[SpirochcFta  pallida,  syphilis  in  man?] 

VII.     Pleuropneumonia. 

The  infectious  agent  of  contagious  pleuropneumonia  of  the 
cow. 

VIII.   Epidemic  Diseases   Caused  by  TJltramicroscopic  Agents. 

Contagium  of  foot  and  mouth  disease,  in  cattle,  swine,  sheep, 
and  transmissible  to  man. 

Contagium   of   cattle   plague. 

Contagium  of  smallpox  in  man,  transmissible  to  cow,  horse, 
rabbits. 

Contagium  of  sheep  pox. 

Contagium  of  rabies  of  dog,  transmissible  to  man  and  all 
mammals. 

Contagium  of  Lombardy  chicken  plague. 

IX.     Diseases  Due  to  Flagellata.  Piroplasmata  and  Sporozoa. 

Trypanosoma  Evansi,  surra  in  domestic  animals  in  India. 
"  Brucei,  nagana  in  African  animals. 

"  eqniperduni,  dourine  in  horse. 


76  Causes  of  Disease. 

Trypanosoma  Theileri,   African   cattle   plague. 

[  "  Gamhiense,   African   sleeping   sickness   in   man.] 

Plasmodium  malaria  equorum,  African  equine  malaria. 

[Plasmodium  of  human  malaria — tertian,  quartan  and  a^stivo- 
autumnal  types.] 

Piroplasma  bigcminum,  epidemic  haemoglobinuria  of  cattle, 
deer  and  sheep. 

Piroplasma  caninum,   infectious   jaundice  of  dog. 

Sarcosporidia  major  and  minor,  parasites  of  muscle  and  cel- 
lular tissue  in  swine,  cattle,  sheep,  goats  and  horses. 

Coceidium  oviform e.  dysentery  of  cow,  intestinal  and  biliary 
duct  parasite  of  rabbit  (also  in  man  and  dog). 

Diseases  Due  to  Mould  Fungi. 

Moiiilia  eaitdida,  thrush  in  man  and  birds. 

Trichophyton  to)isura}is  (numerous  varieties),  bald  patches  in 
cow,  man  and  dog. 

Achorion  Selionlcinii  (numerous  varieties),  favus  in  man  and 
lower  animals. 

Dermatomyces  gallinarum,  scab  of  cock's  comb. 

Aspergillus  fumigatus,  pulmonary  mycosis  in  birds  (excep- 
tionally in  horse  and  cow). 

Animal  Parasites. 

Food  and  conditions  favorable  to  the  existence  of  a  variety 
of  animals  and  plants  are  afforded  by  the  human  and  animal 
bodies,  both  in  the  fluids  and  tissues,  and,  too,  in  the  nutrient 
ingesta  and  in  the  excretory  and  waste  matter.  When  some  organ- 
ism both  acquires  its  nutrition  and  resides  upon  or  in  the  body 
of  another  individual  the  condition  is  spoken  of  as  parasitism 
(Trapa  along  with ;  <^^-ros.  food).  A  parasite,  therefore,  is  a  form 
of  life  zi'hieh  either  transiently  or  pernianentl\'  lives  upon  or 
in  the  body  of  another  organism  for  the  purpose  of  obtaining  its 
nutritio)i   tJierefrom    (Braun.  Heller). 

According  to  their  origin  from  one  or  other  of  the  two  kingdoms  in 
nature,  they  are  separable  into  vegetable  and  animal  parasites  ;  those  which 
hve  on  the  surface  of  the  body  are  spoken  of  as  ectoparasites  or  external 
parasites  (epiphytes,  epizoa),  those  whose  habitats  are  within  the  body 
as  internal  parasites  or  entoparasites    (entophytes,   entozoa). 

In  the  preceding  chapters  the  discussion  concerned  infestment 


Animal  Piirasilcs.  yy 

by  microorganisnis  ai^prcciablc  only  with  the  aid  of  the  niiero- 
scopc.  the  protophytcs  and  protozoa,  a  condition  spoken  of  as  in- 
fection wlien  leading"  to  disease.  Some  of  these  micfobes  well 
merit  the  name  parasites,  since  the  animal  body  in  which  they 
exist  is  the  source  of  their  nutrition,  but  the  toxic  properties  of 
the  most  of  them  are  so  conspicuous  that  we  are  likely  to  think 
of  these  not  so  much  as  ])arasites,  but  as  comparable  to  poison- 
ous plants. 

A  mmiber  of  forms  of  worms  and  arthropoda  (zooparasites) 
have  gradually  assumed  the  character  of  true  parasites  and  actu- 
ally live  and  subsist  upon  the  body  structures.  ( )ccupation  of  the 
body,  either  externally  or  internally,  spoken  of  as  i)n'asioii 
(iiiz'adcrc,  to  penetrate),  is  apt  to  give  rise  to  a  varied  group  of 
tissue  alterations  and  disease  processes  (invasion  diseases  [iiifest- 
ment]  ).  The  individual  in  which  such  a  zooparasite  finds  shelter  is 
to  be  looked  upon  as  the  host  of  the  parasite.  Some  infest  the  host 
only  for  a  brief  period  as  necessary  for  the  acquirement  of  nutri- 
tion (transiriif  <^r  tcutporary  parasites) ,  or  for  the  time  essential 
for  the  completion  of  one  or  more  stages  of  their  development, 
among  which  groups  respectively  fleas  and  the  larvfe  of  gadflies  are 
examples.  Others  are  persistent  and  pass  their  entire  existence  as 
parasites  (habitual  or  pcniiaiicut  parasites).  The  life  of  this 
latter  type  ma\-  be  passed  in  some  instances  entirely  in  one  host 
(inono.rcnoiis  parasites:  ^bvos,  one;  ^evos,  host),  or  may  be  dis- 
tributed over  several   hosts    (hetero.veiioiis  parasites). 

Invasion  of  a  host  at  times  is  merely  the  result  of  accident, 
in  which  case  the  parasite  is  usually  taken  in  with  food:  in  other 
instances  this  or  that  parasite  may  by  its  own  independent  move- 
ments gain  entrance  into  the  body. 

Parasitism  may  he  referred  to  two  underlying  conditions, 
adaptability  of  the  parasitic  organism  to  the  conditions  of  life  af- 
forded by  the  body  of  the  host  and  the  biological  variability  of  the 
former.  Worms  and  arthropods  which  have  assumed  parasitic  char- 
acteristics undoubtedly  at  one  time  lived  independently  in  nature.  It 
may  be  imagined  that  one  of  these  low  types  of  animals  by  acci- 
dent entered  the  bodv  of  some  higher  animal,  and,  finding  condi- 
tions  favorable  for  the  acqiiiremcnt  of  food,  remained  and  multi- 
plied ;  that  the  offspring,  now  native  to  the  body  of  the  host, 
did  not  again  seek  a  free  state,  but  continued  as  parasites,  being 
from  birth  accustomed  to  the  altered  environments.  Such  sup- 
position is  justified  by  the  fact  that  some  parasites  still  show  rudi- 


78  Causes  of  Disease. 

ments  of  organs  worthless  to  them  in  their  present  form  of  life, 
but  which  were  evidently  inherited  from  their  free-living  ancestors. 
For  example,  in  lingiiatnla  tccnioidcs,  a  permanent  parasite  of  the 
nasal  fossae  of  the  dog,  there  are  rudimentary  feet,  probably 
better  dev^eloped  in  the  free-living  predecessors,  but  stunted  in  these 
parasitic  descendants  from  lack  of  use.  In  the  same  way  may  be 
explained  the  absence  of  wings  in  parasitic  insects ;  for  example, 
sheep  lice  have  probabl\"  developed  through  atrophy  of  their 
wings  from  disuse  of  these  organs,  for  there  are  allied  species  of 
insects  which  are  not  parasitic  and  possess  wings.  On  the  other 
hand,  gradual  adaptation  to  life  upon  an  animal  host  leads  to  the 
acquirement  of  new  peculiarities,  on  the  part  of  the  parasite,  as  a 
transformation  of  masticating  mouth  parts  into  piercing  and 
suctorial  organs  and  the  development  of  special  types  of  organs 
for  attachment  and  holding.  Such  adaptations  and  transforma- 
tions of  structure  are  of  such  common  occurrence  throughout  na- 
ture, even  in  case  of  the  human  body  (formation  of  a  horny  sole 
on  the  back  of  the  foot,  originally  soft,  in  cases  where  from  some 
disease  the  dorsum  of  the  foot  is  turned  down  and  walked  on ; 
transformation  of  the  toes  into  prehensile  organs  by  practice), 
that,  as  it  is  true  in  the  higher  animals,  there  is  no  wonder  that 
it  should  occur  in  these  lower  invertebrates  whose  tissues  are 
much  more  capable  of  such  adaptive  growth.  The  newly  ac- 
quired characteristics  become  fixed  in  the  succeeding  generations 
because  of  heredity  and  because  of  uniformity  in  the  vital  condi- 
tions about  them ;  some  species  which  have  gradually  assumed 
parasitic  nature  are  finally  restricted  entirely  to  a  parasitic  life 
and  are  unable  to  live  in  the  external  world ;  others  pass  only  a 
part  of  their  lives,  a  definite  developmental  stage,  as  parasites,  and 
for  the  rest  of  their  time  live  independently.  There  are  certain 
filarial  worms  which  ordinarily  live  in  moist  earth,  but  which  now 
and  again,  as  necessity  arises,  become  parasitic.  As  the  moisture 
disappears  these  worm  retreat  into  depressions  where  the  moisture 
is  longest  retained,  but  should  a  snail  or  earth-worm  happen  in 
their  way  they  pick  out  the  cavities  of  these  animals  and  creep 
into  them.  In  protracted  drouths  they  are  parasitic  for  a  corre- 
spondingly long  period,  and  it  has  been  observed  that  in  such 
parasitic  existence  they  attain  unusual  size  and  produce  a  larger 
number  of  ova  than  their  free-living  fellows  (Braun,  Heller).  It 
may  be  that  the  young  brood  continue  in  the  snail  and  become 
completely  transformed  into  parasites,  but  the  original  ones,  when 


Animal  Parasites.  79 

wet  weather  returns,  abandon  their  parasitic  hiding  places.  L. 
Oerley  has  succeeded  in  artificially  causing  a  free  species  of  worm 
(rhabditis  pellio)  to  live  temporarily  as  parasites  by  introducing 
them  into  the  vagina  of  mice,  where  they  continued  to  live  and 
multiply,  although  when  placed  in  the  digestive  canal  they  died  or 
were  expelled.  Larvae  of  flies  often  resort  to  parasitism  as  oppor- 
tunity is  afforded;  meat  flies  and  other  insects  which  are  ordinar- 
ilv  saprophagous  often  oviposit  upon  some  animal  in  wounds  or 
ulcers  and  the  resultant  maggots  obtain  their  nutrition  in  the 
same  location  as  parasites,  although  succeeding  generations  con- 
tinue as  usual  under  other  conditions  of  existence.  It  may  be 
supposed  that  frequently  such  assumptions  of  a  parasitic  existence 
are  brought  about  by  the  force  of  circumstances  and  end  with 
the  death  of  the  organism  if  it  be  incapable  of  adaptation,  even  if  it 
should  succeed  in  getting  nourishment  from  the  body  of  the  ani- 
mal host.  Only  in  case  the  intruding  worm  (or  other  form  of 
life)  can  successfully  withstand  the  mechanical  and  chemical  influ- 
ences which  oppose  it,  only  in  case  it  obtains  a  habitat  where  it  is 
possible  for  it  to  live,  is  it  likely  to  be  changed  into  a  parasite. 

Some  worms  may  be  -parasitic  in  different  animal  species; 
trichinella  is  parasitic  in  man,  hog,  rat,  mouse,  cat.  fox,  polecat 
and  bear,  and  may  be  artificially  induced  to  infest  the  dog,  rabbit, 
guinea-pig,  sheep,  horse  and  other  mammals.  In  the  same  way  the 
liver  fluke  is  found  in  a  number  of  species.  Other  parasites,  on 
the  contrary,  occur  in  only  one  fixed  species.  For  example,  tcenia 
solitmi  and  tcciiia  saginata  are  found  only  in  the  human  intestine; 
crassicolis  only  in  the  cat ;  in  the  intestine  of  another  species  they 
die  and  it  is  impossible  or  only  an  exceptional  case  that  they 
should  persist.  Such  exceptions,  however,  do  occur  naturally  as 
well  as  in  artificial  attempts  to  infest.  For  example,  bothrioce- 
phalus  latns,  whose  normal  host  is  man.  is  occasionally  found  in 
the  intestine  of  the  dog;  echynorhynchus  gigas,  a  parasite  of  the 
intestine  of  the  hog,  is  in  rare  instances  met  in  man.  Such  cases 
are  to  be  explained  by  exceptional  opportunities  for  transmission. 

The  influence  of  parasites  upon  the  host  varies  much  accord- 
ing to  their  habits  and  situation.  In  many  instances  the  presence 
of  a  parasite  occasions  no  noticeable  disturbances ;  dogs  may  have 
dozens  of  tapeworms  in  them  without  showing  any  evidence  of 
sickness,  although  in  other  cases  even  a  small  number  of  the  same 
tapeworms  cause  digestive  disturbances.  At  one  time  it  was  sup- 
posed that  some  parasites  were  of  use  to  the  host,  as  the  larvae 


8o  Causes  of  Disease. 

of  one  of  the  gastric  flies  (j^astrophilus  sahttaris — so  named  from 
this  idea)  ;  it  was  thought  that  their  presence  in  the  stomach  and 
small  intestine  of  the  horse  promoted  the  secretion  of  gastric 
juice ;  or  it  was  believed  that  some  parasites  consumed  superfluous 
mucus.  Although  it  is  reasonable  to  suppose  that  some  parasites 
obtain  their  nutriment  from  the  waste  matter  (as  is  true  of  the 
infusoria  and  bacteria  always  present  in  the  stomach  in  rumi- 
nants) and  take  part  in  the  breaking  up  the  intestinal  contents, 
yet  it  is  not  to  be  concluded  that  the  parasitic  worms  and  arthro- 
pods have  any  value  whatever  to  their  host.  On  the  contrary,  the 
animal  host,  if  rid  of  them,  will  tlirive  equally  and  better.  All 
parasites  exert  from  time  to  time  some  harmful  influence,  and 
some  are  death-bearing  guests. 

In  the  first  place,  many  parasites  are  harmful  to  their  host  and 
productive  of'  disease  by  their  wandering  in  the  body  and  their 
movements.  Undoubtedly  the  itching  caused  by  the  crawling  para- 
sites inhabiting  the  skin-surface,  and  often  giving  the  host  no 
rest  day  or  night,  has  some  influence  upon  the  health  ;  here  may 
be  mentioned  the  sheep-lice,  itch-mites  and  the  oxyurides  inhabit- 
ing the  rectum  and  causing  continual  tickling  sensations,  as  per- 
fect torments  which  often  give  rise  to  emaciation  (due  to  the  in- 
crease of  metabolism  following  the  incessant  restlessness  from  the 
itching).  Other  parasites  make  their  way  through  the  tissues  by 
boring,  and  thus  where  any  considerable  number  penetrate  into 
the  organs  cause  tissue  destruction  and  occasion  haemorrhages  and 
inflammatory  lesions  (lesions  produced  by  liver  flukes,  larval  tape- 
worms and  lingiiatulidse).  They  may  give  rise  to  a  great  variety 
of  disturbances,  just  as  any  foreign  bodies  in  a  mechanical  way, 
by  compression  of  tissues,  or  by  obstruction  and  narrowing  of 
tubular  passages,  as  sudden  death  by  invading  the  brain,  paralysis 
by  pressure  on  the  s])inal  cord,  atrophy  of  the  liver  by  growth  in 
its  parenchyma,  blindness  by  penetrating  into  the  eye,  rupture  or 
thrombosis  of  the  larger  blood  vessels,  respiratory  interference  and 
suffocation  by  lodgment  in  the  air  passages  and  lungs,  and  intesti- 
nal obstruction.  The  parasites  adhering  to  the  intestinal  mucous 
membrane  by  booklets  or  suctorial  apparatus  often  produce  re- 
flexly  marked  irritative  or  perhaps  nervous  phenomena ;  and,  too, 
a  toxic  influence  is  to  be  ascribed  to  the  metabolic  products  of  a 
number  of  worms  which  may  be  reasonably  thought  to  explain 
the  occurrence  of  nervous  changes  and  general  loss  of  flesh  (as  in 


Animal  Parasites.  8i 

case  of  echinococcus  cysts,  bothriocephalus  and  teniae*).  Local 
inflammatory  lesions  of  the  skin  and  mucous  membranes  are  the 
result  of  mechanical  injuries  caused  by  a  variety  of  parasites. 

The  amount  of  nutritive  substance  abstracted  by  parasites  from 
the  host  is  to  be  regarded  as  usually  relatively  insignificant. 
Where,  hov/ever,  the  parasites  are  blood-suckers,  the  host  is  placed 
at  special  disadvantage ;  the  smallest  of  the  round  worms,  if  pres- 
ent in  large  numbers,  may  cause  serious  loss  of  blood,  and  per- 
haps the  death  of  the  host.  The  roe.  the  common  deer  and  the 
sheep,  for  instance,  are  uniformly  killed  by  an  anaemia  if  blood- 
sucking strongylidas  infest  the  rennet-stomach.  Whole  flocks  of 
poultry  mav  die  out  when  the  poultry  mite,  dcrmanyssus  avium. 
gets  into  the  hennery  and  infests  the  skin  of  the  fowls  in  vast 
numbers,  feeding  daily  upon  the  blood. 

A  century  ago  our  appreciation  of  the  life  history  of  the  parasites 
and  of  the  diseases  caused  by  them  was  but  vague.  It  is  true  that  most 
of  the  worms  found  in  the  human  alimentary  canal  were  known  to  the 
students  of  natural  history  in  antiquity:  and  as  early  as  the  seventeenth  cen- 
tur>-  itchmites  and  their  relation  with  the  itch  were  fairly  well  known. 
Yet  it  was  for  the  most  part  believed  that  parasites  had  their  origin  in 
inspissated  juices  or  pathologically  altered  parts  of  tlie  human  or  animal 
body  by  a  process  of  spontaneous  generation  (gcncratio  ccqutvoca).  When 
the  microscope  came  into  use  and  it  became  possible  to  closely  observe  their 
generative  organs  and  their  products  (eggs),  and  particularly  after  attempts 
came  to  be  made  to  artificially  transmit  the  parasites  by  experimental  feed- 
ing of  the  worms  and  their  larvc-e,  the  real  history  of  their  development  was 
for  the  first  time  apprehended.  Redi  and  Swammerdam,  van  Doeveren  and 
Pallas,  Pastor  Goeze,  C.  Fr.  Miiller,  Bojanus,  Abildgard,  toward  the  end 
of  the  i8th  and  the  beginning  of  the  iQth  century,  Steenstrup,  v.  Baer, 
V.  Siebold,  van  Beneden,  Kiichenmeister,  in  the  middle  of  the  latter 
century,  corrected  the  mistakes  and  hiatuses  of  the  earlier  views  and 
investigated  the  most  interestmg  parasites ;  and  in  recent  years  the  studies 
of  a  large  number  of  zoologists,  physicians  and  veterinarians  (Leuckart. 
Zenker,  M.  Braun,  Peroncito,  Grassi,  Railliet,  Heller.  Ziirn.  L.  G.  Neumann. 
V.  Ratz  and  others)  have  contributed  to  extension  of  our  knowledge  in 
this  field  to  such  a  degree  that  pathology  and  practical  hygiene  have  been 
decidedly   benefited   by   their    investigations. 

♦Persons  handling  ascaris  megalocephala,  the  rouud  worm  of  the  horse,  es- 
pecially if  engaged  in  mincing  it,  are  apt  to  be  directly  affected  by  a  conjunctivitlB 
.-■nd  lu-ticarial  eruption  frrmn  a  certain  substance  cxistinrr  in  the  cu.tlcle  of  tho  worm 
(apparently  a  dermal  secretion)   which  possesses  irritative  properties. 


82  Causes  of  Disease. 


TABLE  OF  PARASITIC  ARTHROPODA  OF  THE  DOMES- 
TIC ANIMALS.* 

I.     Insects  {Insecta). 

1 — Blood-sucking   Flies,    attacking-  the   Skin.     (After    Neumann.) 

Culex  pipiens  (and  other  gnats)  in  man. 

Simulia  reptans,  horse ;  mucous  membranes  of  the  head, 

"         maculatuin,  horse,  ruminants,  man. 
Tabanus  hovinus,  morio,  aiitiimnalis,  bromiiis,  nisticus,  fulvus, 
albipcs,  horse,  ruminants,  man. 

Hcpmatopota  pliiznalis,  horse,  ruminants,  man. 

Chrysops  cacutiens,  horse,  ruminants,  man. 

Stomoxys  calcitrans,  horse, 

Hamatobia  stimulans,  fcrox,  irritans,  serrata,  horse,  ruminants. 

Glossina  morsitans,  horse,  ruminants. 

Hippobosca  equina,  horse,  ruminants,  dog. 

Mclophagus  oz'iniis,  sheep. 

2 — Flies  Parasitic  Upon  or  Beneath  the  Skin  in  Larval  Stage. 

Calliphora   oomitoria,   various  domestic  animals. 
Sarcophaga  carnaria,  magnifica,  JJ'ohlfarti. 
Liicilia  Ccusar,  sericata,  maceUaria. 
Ochromyia  anthropophaga,  dog,  cat,  goat,  man. 
Hypodcrma  lincata,  sheep  [cow]. 

"  tarandi,  reindeer. 

"  hovis,  cow  (even  in  the  spinal  canal). 

"  silenus,  horse,  ass. 

Dermatobia   noxiaUs,   cow,   dog. 

3 — Flies  Whose  Larvae  are  Parasitic  in  the  Intestines  and  Body 

Cavities. 

Gastrophihis  eqiti,  stomach  and  pharynx  of   [horse] . 

"  pecorum,  stomach. 

"  diiodcnalis,  duodenum  of  horse  and  exceptionally 
in  dog. 


•Details  of  the  life-history  and  the  patholog-ical  significance  of  the  species 
enumerated  may  be  found  in  Kitt's  "Lehrhuch  der  Spesiellen,  Pathol.  Anatomic  der 
Haustiere."  [See  also  I'riedberger  and  Frohner,  Veterinary  Pritholonii,  Amer. 
Edition,  'W.  T.  Keener  &  Co.,  Chicago,  1904.) 


Animal  Parasites.  83 

Gastrophilns  hcomorrhoidalis,  stomach,  rectum  of  horse. 

"  flavipes,  stomach  of  ass. 

Oestrus  ovis    {Cephalomyia  oris),  nasal  and  brain   cavities  of 
sheep. 

4 — Fleas. 

Pulcx  irritans,  man,  dog,  cat. 
"       serraticeps,  dog. 
"       goniocephalus,  rabbit. 
"       avium,  chickens,   pigeons   and   other  birds. 

penetrans,  sen  Sareopsylla  penetrans,  man,  domestic  ani- 
mals (tropical). 

Sareopsylla  gallinaeea,  domestic  fowl  in  tropics. 

5 — Lice. 

Hccmatopinus  macrocephalus,  horse. 

"  eurysternus,  cow. 

"  tenuirostris,  cow. 

"  steiwpsu,  goat. 

"  cameli.  camel. 

"  piliferus,   dog. 

"  latus,  dog. 

"  ventricosus,  rabbit. 

6 — Parasites  of  Hair  and  Feathers. 

Trichodcctcs  pilosus,  horse. 

"  panimpilosits,  horse. 

"  scalaris,  cow. 

"  spharoccphalus,  sheep. 

"  climax,  goat. 

"  latus,  dog. 

"  suhrostratus,  cat. 

Melophagus  ovinus,  vid.  blood-sucking  diptera. 
Goniodes    dissimilis,    Burnetii,    Gonioeotes    hologaster,    gigas, 
Lipcurus  variabilis,  hetcrographns,  Mcnopon  pallidum,  biseriatum, 
all  in  the  hen. 

Goniodes  stylifer,  polytrapeaius,  Menopon  biseriatum,  turkey. 
Goniodes    nnmidianus,    rectangulatus,    Lip.    numidice,    Menop. 
numidice,  guinea  fowl. 

Goniodes  falcicornis.   parvieeps,   rectangulatus,  Menop.   phcBOS- 
tonium.  horse. 


84  Causes  of  Disease. 

Goniodes  colchicus,  truncatus,  chrysocephalus,  Lipeurus  varia- 
bilis, Menop.  productiim,  biseriatum,  pheasant. 

Goniodes  minor,  compar,  Lip.  bantlus,  Colpoceph.  longicaudum, 
Men.   lainm,  biseriatum,  pigeon. 

Docophorus  ict erodes,  adustus,  Lipeurus  jejunus,  anseris,  Trino- 
ton  conspiircatum,  continuum,  goose. 

Docophorus  icterodes,  squaUdus,  Trinotum  luridum,  Menopon 
obscurum,  duck. 

Ornithobius  bucephalus,  swan. 

II.     Spiders.      (Arachnoida.) 

1 — Mites.     Parasites  Upon  the   Skin. 

Demodex  sive  Acarus  folliculorum  canis,  cati,  suis,  caprce,  ovis, 
etc.   (in  the  sebaceous  glands  and  hair  folHcles). 

Sarcoptes  major  s.  scabiei  communis,  in  and  beneath  the  epi- 
theHum,  in  horse,  dog,  sheep,  goat,  camel,  monkey,  man. 
Sarcoptes  minor,  cat,   rabbit. 
Dermatocoptes  communis,  horse,  cow  and  sheep ;  also  in  goats. 

"  cuniculi,  in  ear  of  rabbit. 

Dcrmatophagus  communis,  horse,  sheep. 

"  auricularum  felis,  cat. 

"  "  canis,  dog. 

"  "  cuniculi,  rabbit. 

Dermatoryctes  mutans,  fowds,  foot  itch. 
Sarcoptes  lavis,  pigeons  and  fowds. 
Epidermoptes  bilobafus  and  bifurcatus,   fowls. 
HarpirhyncJius  nidulans,  pigeons,  in  the  feather  follicles. 
Hypodcctes  columbarum,  pigeons,  subcutaneous  connective  tis- 
sue and  body  cavities. 

Laminosioptes  cysticola,  fowls,  connective  tissue. 
Cystodites    nudus,    fowls,    pheasants,    air    spaces,    lungs,    liver, 
kidneys. 

Syringophilus  bipectinatus,  fowls,  pigeons. 

'■  uncinatus,  peacocks,  quills  of  feathers. 

Analges  minor,  fowls,  quills  of  feathers. 
Dimorphus  columbce,  pigeon. 
Leptiis  autumnalis,  dog,  man. 

Dermanyssus  avium,  birds,  man,  dog.  cat,  horse,  cow   (ear). 
Gamasus  ptcropoides,  rabbit,  mole,  field  mouse,  cow   (ear). 
Cheyletus  parasitivorox,  rabbit. 


Animal  Parasites.  85 

2 — Ticks.      (Sucking  blood  from  skin.) 

Ixodes  ricinus  and  hexagomis,  man,  dog,  horse,  cat,  ruminants, 
birds. 

BoopJiilus  annulatiis  s.  bozis,  cow   (America). 
Dermacentor  reticulatus,  sheep,  cow,  horse,  man  (America). 

"  clectus,  dog   (America). 

Argas  miniatus,  cow^ 
Amblyonima  americanum,  cow%  man. 

Ornithodorus  Mcgnim,  man,  cow,  sheep,  horse,  ass,  dog. 
Argas  reflexns   s.    marginatus,   pigeons. 

3 — Pentastomes  of  the  Viscera. 

Linguatula  tcenioides,  dog,  wolf,  horse,  goat,  man  (nasal  pas- 
sages). 

Larval  form,  Linguatula  denticulata  (mesenteric  lymph  nodes, 
lungs,  liver),  ruminants,  horse,  cat,  rodents. 

LIST   OF   WOR^IS    PARASITIC   IN    THE   DO:\IESTIC 

ANIMALS. 

I.     Flatworms. 

1 — Tapeworms. 

Anoplocephala  s.  Tccnia  plicata,  horse. 
perfoliata,  horse. 
"  mammillana,  horse. 

Moniccia  cxpaiisa,  ruminants.  :    i 

planissima^  ruminants. 
"         Benedini,  ruminants. 
"         Neumanni,  ruminants. 
"         trigonophora,  ruminants. 
"         denticulata,  ruminants. 
"         alba,  ruminants. 
TJiysanosoma  ortinoides,  sheep. 

"  Giardi.  cow  and  sheep   (hog). 

Sfilcsia   ccntripunctata,   sheep. 
globipuuciata,   sheep. 
Tcriiia   nwrginata.   dog;   bladder   worm,   cysticcrcus   tenuicolUs, 
ruminants  and  hog. 

Tccnia  scrrata,  dog;  bladder  worm,  cysticcrcus  pisiforniis,  hare, 
rabbit. 


86  Causes  of  Disease. 

TcEtiia  echinococciis,  dog,  jackal,  wolf;  bladder  worm,  echinoc- 
occiis  polymorphns,  man,  ruminants,  hog. 

Tceriia  canurus,  dog;  bladder  worm,  co'nurus  cerehralis,  rumi- 
nants, horse. 

Dipylidium  caninum^  (Taenia  cucumerina),  dog,  cat,  man; 
bladder  worm,  cryptocystis  tricJiodectis  et  pulicis,  larvae  of  dog 
fleas  and  ticks. 

Mesocestoides  lineatus   (Taenia  litterata),  dog,  fox,  cat. 

Tcenia  serialis.  dog ;  bladder  worm,  cysticercus  s.  coenurus  seri- 
alis,  rabbit. 

Tcenia  Krabhei,  dog;  bladder  worm,  cyshcerciis  tarandi,  rein- 
deer. 

Bothriocephadus  lotus,  man.  dog,  cat ;  larva,  plerocercoid  of 
fishes. 

Bothriocephalus  cordatiis  and  fusciis,  dog. 

Tauia  crassicollis,  cat ;  bladder  worm,  cysticercus  fasciolaris, 
mouse. 

Dipylidium    Chyzeri.    PasquaJi.    Trinchcsii,    cat. 

Tcenia  solium^  man ;  bladder  worm,  cysticercus  ceJluloscB,  hog, 
dog,  cat,  sheep,  roe,  polar  bear,  rat,  man. 

Tcenia  inerniis  hoin.  s.  niediocanellata  s.  saginafa,  man ;  blad- 
der worm,  cysticercus  inerniis,  cow. 

Drepanidiotccnia    inf undihulif orrnis ,    fowl. 

Dicranotcenia  sphenoides,  fowl. 

Davainca  proglottina. 

"         tetragona,     eesticillus     ectinohothrida,     fowl;    Fried- 
bergeri,  pheasant. 

Bothriotcenia  longicollis,  fowl. 

Drepanidiotcenia  lanceolata,  setigera,  fasciata.  anatina,  gracilis, 
Krabhei,  tenitirostris,  goose  and  duck. 

Dicra>iotcenia   furcigera,   megalops,   eoronula,   duck. 

Mesocestoides   inibuti[ormis,   duck. 

Echinocotyle  Rosseteri,  duck. 

Dazainea  crassnla,  pigeon. 

Bothriocephalus  colunibarum,  pigeons. 

2 — Fluke-worms. 

Fasciola  hepatica.  distoniuni  hepaticuni,  rtmiinants,  hog,  ass, 
horse,  rodents,  man  (liver — errant  examples  in  the  lungs  and 
musculature  ). 


Animal  Parasites.  87 

Fasciola  laiiccolata,  distoimim  s.  dicrocceliiim  lanceolatum,  ru- 
minants, hog,   rodents    (liver). 

Fasciola  magna,  cow,  elk   [deer],   (liver),   (America,  Italy). 

Distomum  truncatum,  alhidiim  and  felineum,  cat   (liver). 

Agamodistomiim  snis,  hog   (muscle). 

Distomum,  echinostomum  alatum,  ducks  and  other  water  fowl, 
exceptionally  dog   (intestine). 

Amphistoma  conicum,  ruminants   (first  stomach). 
"  Collinsi,  horse   (intestine),   (Egypt). 

Gastrodisciis  Sonsinoi,  horse   (intestine),   (Egypt). 

Monostoma  verrucosum,  duck,  fowl,  goose. 
"  attenuatum,  goose  (intestine). 

Distoina  oxycephalmn,  duck,  fowl,  goose   (intestine). 

"  dilatatum,    armatum,    lineare,    ovatum,    commutatum, 

fowl    (intestine). 

Holostoma  erraticum,  duck  (intestine). 

Distomum  hcematohium  s.  crassum  (Bilharsia  crassa),  cattle, 
sheep,  monkey  (urinary  organs,  intestine),  (Mediterranean  bor- 
ders), 

Distoiiiuiii   Westermanni,  cat    [man]    (lungs). 

Distomum  heterophyes,  dog   (intestine),   (Japan). 

Distomum  pancrcaticum,    cow,   sheep,    (Japan). 

TI.     Round  Worms. 

1 — Acanthocephalid  Worms  (Thorn-headed  worms). 
Echinorrhynchus  gigas,  hog,  man    (intestine). 

"  polymorphus,  goose,  duck  (intestine). 

2 — Common  Round  Worms. 

Ascaris  megalocephala,  horse,  ass  (intestine). 
"        mystax,  dog,  cat   (stomach,  intestine). 
"        lumhricoidcs,  man   (intestine). 
"        suilla,  hog  (intestine). 

"        vitidi,  cow  (intestine).  ■' 

"        ovis,  sheep  (intestine). 
Hctcrakis  uujculosa,    pigeon    (intestine). 
"  inflexa,  fowl,  turkey   (intestine). 

"  papulosa  s.  vesicularis,   fowl,  peacock,   guinea   fowl, 

turkey    (intestine). 

Heterakis  diffcrens,   fowl    (intestine). 

"  dispar,  duck,  goose   (intestine). 

Gnathostoma  hispidum,  hog  (stomach). 


88  Causes  of  Disease. 

3— Pin  Worms. 

O.vyuris  7  cniticiihiris,   dog.  man    (rectum). 

ciirvula,  iiiastigodes,  horse   (colon  and  rectum). 
ambigua,  rabbit    (caecum). 

4 — Strongylus   Worms. 

Eustrongylits  gigus,  dog,  horse,  cow  (kidneys,  peritoneum, 
heart,  hver). 

Etistrongylus   tubifc.x,   duck    (intestine). 

Strongylus  anuafus  s.  sclcrostomuui  aruiatuui,  horse  (intes- 
tine) ;  peritoneum  (larvaj  and  embryos  wander  into  the  arteries, 
brain,  testes)  ;  str.  arniatus  has  recently  been  subdivided  by 
Sticker  into  three  species:  Sclcr.  edentatum,  hidentatum,  quadri- 
dcntatum. 

Strougylus  tctracaiitJius  (sclerosf.  tctr.),  horse  (large  intes- 
tine). 

Strongylus  contort us^    ruminants    (abomasum,   small    intestine). 
Ostertagi,  cow,  sheep,  goat  (abomasum). 
Ciirticci,  cow,  sheep  (abomasum,  small  intestine). 
oncophorus,  cow   (abomasum,  small  intestine). 
Harkeri,  cow    (abomasum). 

rctortcrformis,  ruminants,  hare,   rabbit    (abomasum, 
small   intestine).  * 

Strongylus  lilicollis,    sheep    (small   intestine). 
radiatus,  cow   (small  intestine). 
inflatus,  cow   (colon). 
.-I.vci.  ass    (stomach). 
Iiypostoiuus,  sheep,  goat   (intestine). 
filar ia,  sheep,  goat,  fallow  deer,  red  deer   (bronchi, 
lungs). 

Strongylus  parodo.vus.  hog,  sheep   (bronchi,  lungs). 

coin.niutatus,  sheep,  goat,  hare   (lungs,  bronchi). 
micrurus,  cow,  horse,  red  deer,  fallow  deer    (bron- 
chi, lungs). 

Strongylus  Amficldii,  horse    (lungs). 

sagittatus,  red  deer    (lungs). 

capillaris,  goat,  sheep,  chamois   (bronchi,  lungs). 
den  tat  us,  hog  (large  intestine). 
"  ruhidus,  hog    (America). 

annidatus    {Strong,    s.   Filaria   tracheo-hronchialis) , 
dog  (air  passages). 


A  III  III  a  I  Parasites.  89 

Strongylus  vasoruin   canis,   dog    (blood    vessels). 
"  pussihis^  cat   (lungs). 

"  tenuissimiis,  horse  (stomach). 

"  Icporum,  hare,,  rabbit   (stomach),    (America). 

"  tenuis,  goose   (caecum). 

"  nodularis,  goose  (pharynx). 

"  s.  Syngamus  trachealis,  hronchialis,  fowl,  pheasant, 

horse,   goose,   duck,   etc.    (air  passages). 

Dochinius  trigonoccphahts,  dog,  cat  (intestine). 
stenocephahis,  dog   (intestine). 
"  tubceformis,  cat  (intestine). 

"         boz'is    s.    CEsophagostoma    vcsiculosuui,    cow    (intes- 
tine). 

CEsophagostoiiia  colninbiaiiuin,  sheep,  deer    (intestine). 
Uncinaria  cernua,  sheep,  goat   (intestine). 
Olhdanits  tricuspis,  cat  (stomach,  embryos  in  the  lung). 
Strongyloides  intestinalis  s.   Anguillula  stercoralis,   man,   fowl 
(intestine). 

Anguillula  vivipara,  horse    (colon). 
Rhabdoncnia   longum,   sheep,   hog    (intestine). 

5 — Whip   Worms. 

Tricocephaliis  dispar,  man,  dog. 

"         affinis,   ruminants    (large  intestine). 
"         crcnatus,    hog    (large   intestine). 
"         depressiuscitliis,    dog    (large    intestine). 
Trichosoina  ccropliUnm.  cat    (trachea,   bronchi). 
fclis  cati,  cat    (urinary  bladder). 
longicoUc,   fowls    (csecum  and   rectum). 
"         aniiulotnrn,  fowls    (pharynx). 
"  coiitortnin,  duck    (crop,   pharynx). 

"         collar e,   fowls    (intestine). 

"         tcnuissiiiiiiiii    and    brevicoUc,    pigeon     (small     intes- 
tine). 

Trichina  spiralis,   hog,   rat.   man,   all   carnivora    (intestine,   em- 
bryos and  undeveloped  trichinelke  in  muscle). 

6 — Filariae. 

Filaria  papulosa  s.   equina,  horse    (peritoneum,  pleura). 
tercbra,  cow,  deer  (peritoneum,  eye). 


90  Causes  of  Disease. 

Filaria  lacrymalis,  horse,  cow   (conjunctival  sac). 
"       imniitis,  dog    (heart)    (Asia    [America]). 
"       s.  Spiroptera  sanguinolenta,  dog   (stomach,  aneurisms, 
pharynx). 

Filaria  s.  Spiroptera  strongylina,  hog   (stomach). 

"  s.  Spiroptera  megastoma  and  microstoma,  horse  (stom- 
ach) ;  Gongylonema  scutatiim,  sheep,  cow,  horse  (pharynx)  ; 
Gongylonema  pulchrum,  hog   (pharynx,  tongue). 

Filaria  s.    Onchocerca  reticulata,   horse    (tendons,   ligamentum 
nuchse). 

Filaria  hceniorrhagica,  horse    (skin). 
DermoHliaria  irritans,  horse  (skin). 
Filaria  uncinata,  goose    (pharynx,  crop,  intestine). 
"       nasnta,  fowl    (crop). 

*'       s.  Dispharagits  spiralis,  fowl   (pharynx,  crop). 
Tropidocera  inflata,  duck   (crop). 

7 — Annelides. 
Hcemopis  sanguisuga,  horse   (pharynx). 


COURSE  AND  TERMINATION  OF  DISEASE; 
SYMPTOMATOLOGY;  DIAGNOSIS 

The  disturbances  of  function  which  indicate  the  existence 
of  disease,  as  well  as  anatomical  or  chemical  organic  changes,  are 
spoken  of  as  the  signs  or  symptoms  of  disease;  the  branch  of 
study  dealing  with  these  as  semeiology  or  symptomatology 
{t6  <7r),xdov  from  ai)iJ.aivui,  to  denote  ;  (Jv^x-lvl^^TeLv,  to  happen  with,  that 
is,  in  connection  with  certain  disease  states).* 

The  art  of  concluding  from  symptoms  the  existence  of  definite 
morbid  changes  in  the  body,  of  determining  the  nature  and  loca- 
tion   of    disease,    is    known    as    Diagnosis    or    establishment    of 
a  diagnosis  (i,  d^dy,u,^is,   differentiation     or    thorough    knowledge; 
from    7a•"i'T^-«^      ^o    recognize).    Formerly    when    the    anatomical 
and  chemical  faults  which  underlie  disease  were  unknown  it  was 
deemed  sufficient  for  the  physician  to  merely  appreciate  the  ex- 
ternal manifestations  of  disease,  and  such  terms  as  dropsy,  jaun- 
dice,  fever  and  marasmus   were   used   without   attempt   at  nearer 
approach   to   the   causes   of   these   symptoms.      Even   to-day   there 
may  now  and  again  be  times  when  it  is  necessary  to  rest  satisfied 
with  no  more  than  such  a  symptomatic  diagnosis.     However,  as 
far  as  it  is  possible  to  conclude  from  symptoms  that  definite  ana- 
tomical  changes   exist,   or   as    far   as   such   are   directly   manifest, 
we  are  accustomed  in  these  days  to  make  anatomical  diagnoses; 
and  as  far  as  it  is  possible  to  determine  the  development  of  any 
aft'ection,    to    make    also    an    (etiological    diagnosis.      The    aim    of 
modern  diagnosis   is   the   study   of   the   disease   from  all   three   of 
these  points  of  view  and  the  appreciation  of  the  condition  of  all 
the  organs  in  their  relation  to  each  other,  so  as  to  permit  of  the 
recognition    of   how    a    given    local    condition    must    influence    the 
rest  of  the  organs  of  the  body  generally. 

'The    prlnclpaT  features    of    tbls    chapter    have    been    In    Part    adapted    from 
Handbuch  der  aUgem.     Pathologie,  Fhl  und  Wagner  (Leipzig,  1870). 


92  Symptomatology;    Diagnosis. 

A  purely  symptomatic  diagnosis  is  illustrated  by  such  examples  as 
the  determination  of  varieties  of  convulsions,  of  palpitations,  coughs ;  a 
symptomatic  and  anatomical  diagnosis,  by  the  recognition  of  a  relation 
existing  between  jaundice  and  some  hepatic  affection;  an  ^etiological  diag- 
nosis, by  the  conclusion  that  a  jaundice  depends  upon  the  presence  of 
some  microorganisms  in  the  liver  and  blood.  [Very  frequently  diagnoses 
are  classified  as  topographical,  when  indicating  the  location  and  extent  of 
lesions,  and  as  nosological,  when  indicating  the  nature  of  the  process. 
No  diagnosis  can  be  regarded  as  complete  unless  embodying  the  recogni- 
tion of  both  location  and  nature  of  an  affection,  as  well  as  of  its  aetiology, 
in  so  far  as  is  possible.  Incomplete,  purely  topographical  diagnoses,  as 
the  declaration  of  "lung  disease,"  "kidney  disease,"  etc.,  are  often  made 
to  serve  the  nonce,  or  by  the  careless  as  final ;  in  the  same  way  an  incomplete, 
merely  nosological  diagnosis  is  often  met  with  where  it  is  said  that  an 
individual  is  the  subject  of  "inflammation,"  "congestion,"  "dropsy,"  "fever," 
"tuberculosis."  The  full  diagnosis  should  declare  that  the  subject  has 
an  inflammation  of  the  pericardium,  if  possible  indicating  the  cause  of 
the  pericarditis ;  "tuberculous  caseation  of  the  lungs"  would  embody  all 
the  desirable  points  of  view.] 

Symptoms  immediately  referring  to  changes  in  a  given  part, 
as  abnormality  of  color,  increased  size,  hardness,  softness  or  un- 
evenness  of  outline,  are  spoken  of  as  direct  symptoms;  those 
which  do  not  depend  upon  the  diseased  organ  entirely,  but  which 
perhaps  may  be  appreciable  in  the  products  of  such  an  organ  or 
become  manifest  in  other  organs  in  relation  with  the  diseased 
part,  are  known  as  indirect  symptoms.  Thus  a  direct  symptom 
of  a  lesion  of  one  of  the  cardiac  valves  would  be  a  cardiac  mur- 
mur;  an  indirect  symptom  of  pericarditis  would  be  an  oedema 
of  the  dewlap.  There  are  certain  symptoms  called  pathognomonic 
sympfouis,  whicli  definitely  indicate  the  existence  of  some  particu- 
lar disease,  as  the  rusty  nasal  discharge  in  pneumonia,  locking  of 
the  jaws  in  tetanus,  crepitus  at  the  site  of  a  fracture  of  bone; 
however,  as  a  rule  a  single  symptom  does  not  suffice  for  a  diag- 
nosis, but  must  be  considered  in  its  relations  with  a  wider  group 
of  recognized  features.  Study  of  disease  phenomena  constitutes 
a  large  part  of  clinical  pathology  and  pathological  anatomy;  tho 
ability  to  recognize  and  to  determine  the  im.portance  of  symptoms 
is  one  of  the  essentials  of  the  medical  art.  and  depends  on  the 
skill,  experience,  general  knowledge  and  power  of  judgment  of 
the  individual  conducting  the  examination  of  the  subject.  The 
majority  of  symptoms  can  be  realized  only  by  special  methods 
of  examination.  He  who  has  not  acquired  such  methods  cannot 
have  a  clear  understanding  about  the  morbid  condition  extant 
in  the  body  of  his  patient,  and  is  really  groping  about  in  the  dark- 


f  j 


Diagnosis.  93 


ness.     Eye,  ear  and  sense  of  touch,  partly  unaided,  partly  aided 
by   instruments   of   precision   and   special   technical   methods    (em- 
ployment   of    reflecting    mirrors    for    illumination,    of    instruments 
used  in  percussion  and  auscultation,  of  methods  of  mensuration, 
weighing,   thermometry,  microscopy  or  chemical  tests)    contribute 
to  our  power  of  appreciation  of  the  signs  of  disease.     With  ex- 
perience   it    is    possible    that    the    examiner    at    a    single    glance 
(diagnosis   at   a   distance)    may   recognize   some  types   of   disease, 
some    forms    which    manifest    themselves   by    sharply    marked    ex- 
ternal   features   appreciable    even    at    a   hasty    inspection.      Other 
morbid    conditions     may    be    more   or   less   correctly   conjectured 
from  the  information  given  by  some  person  from  his  observation 
of    the    patient    (diagnosis    from    the    aiiaiiiitcsis:    ava-ixifj-vriffKO},    to 
recollect).     Both  methods  are  open,  however,  to  serious  error  if 
practiced  alone,  being  based  on  incomplete  data  and  imperfect  in- 
vestigation;    and    although    practical    experience    with    quick    per- 
ception   of    frequently    observed    facts    may    often    arrive    at    the 
truth  by  such  methods,  only  careful  objective  study  will  guaran- 
tee an  absolutely  certain  diagnosis.     In  order  to  gain  a  compre- 
hensive idea  of  the  pathological  process  presented,  it  is  essential 
not   only   to   consider   the    functional    disturbances    of    one    single 
part  of  the  body,  which  is  apparently  the  seat  of  the  disease,  but 
to  systematically  inquire  into  the  condition   of  every  part  of  the 
economy  and  every  function. 

(For  fuller  discussion  of  these  points  the  reader  is  referred 
to  Friedberger-Frohner.  Lchrhncli  dcr  kliiiiscJicii  Unfersiicliuiigs- 
methodcn,  or  ^loller,  Klin.  Diag.  dcr  dusscni  KraiikJicHcii  dcr 
Haitsticrc.  F.  Enke,  publisher.) 

The  art  of  diagnosis  concerns  itself,  after  the  proper  recog- 
nition of  the  symptoms  manifested,  with  the  condition  of  the 
oreans,  finallv  reaching  a  definite  conclusion  through  processes 
of  comparison  of  the  features  appreciated  with  the  commonly  ac- 
cepted pathology  of  known  diseases.  All  possible  affections  are 
carefully  considered,  the  symptoms  presented  by  the  subject  con- 
trasted wath  those  of  each  different  known  disease,  and  determina- 
tion of  the  aft'ection  attempted  from  the  strongest  features  of 
correspondence. 

[In  systematic  study  of  a  given  case  it  is  well  to  follow  some 
routine  of  investigation.  Thus  commonly  one  takes  into  consider- 
ation such  general  features  as  the  age,  sex,  race  or  species  of  the 
subject,  the  general  surroundings  and  habits  of  life  and  features 


94  Course  of  Disease. 

bearing  on  questions  of  heredity;  subsequently  the  general  pre- 
vious medical  history  of  the  subject,  the  anamnesis,  is  taken  up, 
and  a  study  of  the  known  features  of  the  present  attack  in  its 
development.  Thereafter  is  made  a  close  and  complete  objective 
study  of  the  subject,  this  including  as  thoroughly  as  possible  the 
whole  body,  the  condition  of  every  organ  by  the  methods  of  ordinary 
physical  diagnosis  and  the  more  elaborate  methods  of  clinical 
technology.  Given  such  data  one  should  be  able  by  his  patho- 
logical training  to  recognize  the  seat  of  the  affection  and  the 
extent  of  its  distribution  in  the  body,  the  topographical  diagnosis, 
and  the  nature  of  the  affection,  the  nosological  diagnosis.] 

The  establishment  of  a  diagnosis  leads  directly  to  prognosis 
and  therapeutic  application.  By  the  term  prognosis  is  meant  the 
foretelling  of  the  mode  of  development  [the  order  of  the  events 
in  the  course,  and  the  duration  of  the  disease]  and  termina- 
tion (whether  favorable,  prognosis  faiista ;  unfavorable,  prognosis 
infansta ;  or  uncertain,  prognosis  anccps).  The  course  and  ter- 
mination of  many  diseases  may  be  predicted  with  more  or  less 
certainty,  inasmuch  as  examples  of  the  aft'ections  are  constantly 
occurring  and  an  experienced  physician  is  quite  familiar  with  their 
development  and  modes  of  progress.  The  prognosis  must, 
however,  in  a  measure  depend  upon  each  individual  case,  its 
special  constitutional  peculiarities,  the  degree  of  general  involve- 
ment of  the  bod}'  and  the  distribution  of  the  disease-changes,  the 
vital  importance  of  the  affected  organ,  the  variations  of  the  disease 
from  its  usual  trend,  the  complications  and  the  possibility  of  em- 
ploying proper  remedial  measures. 

Therapeutics  (i)  Oepawela,  from  eepairevco,  to  serve  or  cure)  or 
remedial  treatment  has  to  deal  with  eft"orts  directed  toward  com- 
pensation for  and  removal  of  disease.  Where  it  is  possible  by 
definitely  conceived  measures  to  remove  the  basic  fault,  the 
anatomical  alterations  and  the  causative  influence  underlying  the 
morbid  condition,  therapy  manifestly  becomes  rational  or  radical; 
where  it  is  possible  only  to  combat  symptoms  (pain,  fever)  it  is 
said  to  be  symptomatic  treatment,  which  at  best  is  but  a  tempo- 
rary means  or  measure  of  relief  (paUiative,  from  pallium,  a  cloak 
or  protection). 

The  duration  and  course  of  diseases  depend  closely  upon  their 
causes  and  upon  the  extent  and  nature  of  their  basic  structural 
alterations.  Some  diseases  are  sudden  in  their  onset,  last  but  a 
few  minutes  or  hours,  and  terminate  in  the  death  of  the  individual 


Diagnosis.  95 

or  in  a  rapid  disappearance  of  the  various  lesions.  The  former 
type  includes  such  conditions  as  wounds,  lacerations  of  external 
or  internal  parts  or  the  effects  of  poisons  which  rapidly  and  com- 
pletely destroy  the  function  of  vital  organs ;  the  latter,  character- 
ized by  rapid  recovery,  is  met  in  disturbances  which  are  not  fol- 
lowed by  structural  changes,  as  convulsions,  ansemic  and  hyperae- 
mic  states  of  the  brain,  of  the  skin  and  of  mucous  membranes. 
On  the  other  hand,  diseases  may  continue  for  weeks  or  months,  or 
even  years.  They  may  begin  suddenly  or  gradually  and  insidiously  ; 
may  manifest  alternately  intensity  and  diminution  in  the  severity 
of  their  symptoms,  fluctuations  in  the  morbid  processes  (remis- 
sions and  exacerbations)  ;  may  invade  suddenly  {paroxysmal; 
paroxysm,  invasion)  and  present  interruptions  {intermittent)  in 
the  course,  sometimes  ending  with  gradual  improvement  {lysis, 
resolution) ,  sometimes  in  a  rapid,  abrupt  change  {crisis,  decisive 
stage),  leading  to  recovery  or  death.  [By  the  course  of  the  dis- 
ease is  meant  the  order  of  manifestation  of  the  various  stages  or 
events  of  the  disease.  It  may  be  definite,  regular  or  acute  on  the 
one  hand,  when  its  events  proceed  in  orderly  manner  and  come  to 
a  definite  termination,  or  it  may  be  indefinite,  irregular  or  chronic, 
when  there  is  no  fixed  order  of  events  and  there  is  no  set  limita- 
tion. Among  the  different  types  of  the  regular  course  two  major 
forms  are  recognized:  (a)  the  continued  course,  where  there  is 
but  little  variation  in  the  intensity  of  the  symptoms  from  time  to 
time,  and  (b)  periodic  courses,  in  which  at  certain  definite  times 
special  events  manifest  themselves.  Among  the  periodic  courses 
are  met,  intermittent  forms,  in  which  there  alternate  periods  of 
absence  of  symptoms,  known  as  intermissions,  with  periods  of 
presence  of  the  symptoms  in  their  intensity  or  paroxysms ;  remit- 
tent forms,  in  which  there  alternate  periods  of  intensity  of  symp- 
toms, known  as  exacerbations,  with  periods  of  diminution  in  in- 
tensity, known  as  remissions ;  and  recurrent  forms  in  which  there 
alternate  comparatively  long  periods  of  absence  of  symptoms,  the 
intermissions,  with  similarly  prolonged  periods  of  their  presence, 
recurrences.  The  last  form  differs  from  the  first  in  the  length  of 
the  alternating  periods.] 

Diseases  of  brief  duration  are  called  acute  diseases;  those  of 
prolonged  course,  chronic.  The  former  may  last  for  a  variable 
period,  up  to  fourteen  days,  while  the  latter  extend  over  a  course 
of  more  than  forty  days :  any  instances  falling  between  these 
durations    mav    be    classed    as    sub-acute    affections.     In    case    of 


g6  Course  of  Disease. 

diseases  which  ordinarily  continue  for  a  year  or  more,  a  shorten- 
ing of  the  course  to  a  few  months  manifestly  fixes  such  duration 
as  an  acute  one,  as  in  case  of  tuberculosis,  glanders  or  rickets. 
[The  terms  acute  and  chronic  have  really  a  less,  limited  signifi- 
cance than  the  author  here  applies  to  them ;  they  each  have  in  one 
sense  a  reference  to  the  length  of  the  course,  but  in  addition  refer, 
perhaps  without  desirable  clearness,  to  the  possibility  of  recovery 
and  the  intensity  of  symptoms  and  the  order  of  events  in  the 
course.  In  the  matter  of  time  it  is  scarcely  possible  to  give  any 
fixed  number  of  days,  or  even  months,  to  the  terms.  Each  dis- 
ease is  a  law  unto  itself,  and  only  in  the  broadest  way  may  we 
say  that  an  acute  course  is  one  of  brief  duration.  But  in  addi- 
tion, when  we  apply  this  term,  we  mean  that  whatever  the  actual 
duration,  at  any  rate  the  disease  will  come  to  a  definite  Umit ;  and, 
moreover,  w^e  expect  the  course  to  follow  more  or  less  closely  a 
given  order  in  the  manifestation  of  its  symptoms,  and  believe 
there  is  a  chance  of  recovery.  In  case  of  chronic  diseases  again 
we  cannot  set  a  fixed  limit  of  days,  months,  or  even  years,  which 
shall  declare  the  course  to  be  a  chronic  one.  (Thus,  while  alienists 
are  inclined  to  set  a  limit  of  a  year  to  cases  of  mania  or  melan- 
cholia, and  to  call  all  cases  chronic  if  of  longer  duration,  there 
really  are  no  appreciable  dififerences  in  many  instances  of  even 
longer  duration  from  their  condition  within  the  first  few  weeks  of 
insanity.)  Moreover,  when  a  case  is  declared  chronic,  while 
there  is  no  actual  assertion  to  this  effect,  nevertheless  there  is  a 
feeling  of  hopelessness  as  to  the  chance  of  recovery ;  the  termina- 
tion looked  for  is  rather  death,  and  that  at  an  indefinite  time.  No 
exact  order  of  symptom  presentation  is  expected  in  such  chronic 
cases.  Finally,  while  there  are  often  exceptions  to  this  point, 
in  general  the  severity  of  the  symptoms  of  an  acute  case  is  apt  to 
be  greater  than  in  a  chronic  form  of  the  same  disease.] 

Diseases  often  show  [especially  those  of  an  acute,  regular  or 
definite  type  of  course]  a  succession  of  definite  periods  or 
stages  in  which  certain  phenomena  appear,  which  are  empirically 
expected  and  whose  development  is  awaited  with  the  progression 
of  the  anatomical  changes.  These  diseases  are  said  to  have  a 
typical  course.  [A  regular  or  definite  course  is  well  illustrated  by 
the  acute  infectious  fevers,  in  which  the  following  periods  may 
be  recognized  in  the  order  named:  (a)  infection  (time  of  en- 
trance of  the  microbic  cause),  (b)  incubation  (a  period  without 
symptoms,    l)ut    during    whicli    the    .germs    are    multiplying    in    the 


Stages  of  Disease.  97 

economy  to  sufificicnt  number  to  excite  their  definite  elTects),  (c) 
prodrojiics  (a  period  of  indefinite  and  usually  slight  symptoms, 
the  first  and  as  yet  more  or  less  obscure  evidences  of  the  presence 
of  microbes  in  the  system),  (d)  invasion  (the  period  of  develop- 
ment of  tlie  specific  symptoms  of  the  afifection  ;  this,  if  it  occur 
rapidly,  is  said  to  be  a  fnuik  iiiiasioii;  if  gradually,  is  called  an 
insidious  iivz'asioji),  (e)  acme  or  fastigium  (the  period  of  fullest 
intensity  of  the  disease),  (f)  occasionally  an  amphibolic  sta^c  (a 
period  of  uncertainty  and  marked  variation,  corresponding  to  the 
popular  idea  of  crisis  and  used  by  the  author  above  in  this  sense), 
(g)  decline  (period  of  disappearance  of  the  disease;  this,  if  it 
occur  rapidly,  is  said  to  be  "by  crisis;"  if  slowly,  "by  lysis''),  (h) 
finally,  not  as  a  true  stage  of  the  disease,  but  a  definite  period 
before  health  is  resumed,  convalescence  (period  of  repair  and  re- 
building of  structures  destroyed  or  impaired  in  the  course  of  the 
affection,  and  of  resumption  of  efficient  function  by  the  various 
parts  of  the  body).  If  the  cause  of  an  acute  disease  be  not  a 
vital  one  the  course  includes,  of  the  above  stages,  only  those  of 
invasion,  acme,  decline  and  convalescence.] 

However,  in  such  well-known  affections,  as  a  result  of  special 
etiological  factors  or  the  accidental  interference  of  external  in- 
fluences, variations  (irregitlarities)  may  occur,  rendering  the 
course  an  atypical  one.  In  case  the  symptoms  remain  for  a  long 
time  of  uniform  type  and  intensity,  without  appreciable  ameliora- 
tion or  increase,  the  disease  is  said  to  be  stationary. 

Latent  diseases  are  those  which  do  not  manifest  themselves, 
either  at  all  or  in  part,  in  certain  phases  of  their  development. 
This  depends  upon  either  the  impossibility  or  difficulty  of  proper 
examination  of  the  organs,  which  are  the  seat  of  the  disease  (as 
the  pancreas  or  some  parts  of  the  lung),  or  upon  the  fact  that  the 
disease  is  so  localizefl  or  has  been  so  gradual  in  its  development 
that  the  function  of  the  organ  has  not  been  materially  affected. 
Latency  is  often,  therefore,  only  a  temporary  or  transient  feature, 
and  it  is  often  correct  to  speak  of  a  latent  stage  and  of  a  later 
m.anifested  or  open  stage.  Some  diseases,  even  though  they  be 
severe,  remain  latent  because  they  are  foUowed  by  adaptations 
(compensatory  conditions)  which  entirely  prevent  their  usual 
symptoms,  as  when  a  valvular  lesion  of  the  heart  is  followed  by 
compensatory  cardiac  hypertrophy. 

When  a  disease  is  characterized  merely  by  local  symptoms  and 
alterations  it   is  known   as  a  local  disease  or  disease   of   [this  ov 


98  Course  of  Disease. 

that]  organ;  if,  however,  a  number  of  organs  are  involved  and 
their  functions  interfered  with,  and  if  the  general  economy  is  ap- 
parently affected,  the  condition  is  spoken  of  as  a  general  disease 
or  a  disseminated  (generalized)  disease.  (Examples  of  general 
disease  are  met  with  in  such  alterations  as  provoke  general 
metabolic  disturbances  and  abnormalities  in  the  composition  of  the 
blood.  Formerly  the  term  constitutional  disease  or  dyscrasia,  de- 
composition of  the  blood,  was  used  in  this  connection.)  Funda- 
mentally there  is  no  distinction  in  these  terms,  but  as  a  rule  the 
term  dissemination  has  special  reference  to  a  multiplication  of 
local  lesions,  to  an  extension  of  the  causes  of  the  disease  to  a 
number  of  situations  where  new  foci  of  the  same  type  appear,  or 
to  a  reaction  of  a  functional  disturbance  of  one  organ  upon  the 
rest  of  the  system.  For  example,  a  prolonged  disturbance  of  the 
function  of  the  kidneys  will  give  rise  to  a  disturbance  in  the 
cardiac  action  and  retention  of  harmful  products  of  metabolism ; 
or,  as  in  the  case  of  tuberculosis,  the  infectious  agencies  pass 
from  the  original  local  focus  into  the  lymph  and  blood,  extend  by 
direct  growth  into  the  surrounding  organs,  and  in  various  scat- 
tered foci  in  the  body  to  which  they  have  been  conveyed ;  the  dis- 
ease thus  becoming  disseminated  and  generalized.  Some  affec- 
tions, on  the  other  hand,  at  first  manifest  general  symptoms 
(fever),  later,  however,  showing  distinct  evidence  of  their  purely 
local  type.  Variations  in  the  course  of  disease  may  also  depend 
upon  the  predisposition  characterizing  the  animal  species  in  ques- 
tion, as,  for  example,  is  seen  in  case  of  glanders  in  field  mice,  an 
acute  septicemic  affection,  in  contrast  to  the  same  disease  in 
horses,  where  it  is  usually  a  chronic  local  affection,  gradually  ex- 
tending through  the  system. 

The  local  lesions  which  first  arise  from  the  operation  of  a 
pathogenic  agency  are  known  as  primary  lesions,  those  which  fol- 
low as  secondary.  The  action  of  such  an  agency  may  be  confined 
to  one  locality,  the  lesions  disappearing  after  its  removal,  as  in 
case  of  corrosion,  heat  action  or  traumatism.  The  generalization 
usually  depends  directly  upon  the  spread  of  the  pathogenic  influ- 
ences through  the  body,  and  may  therefore  take  place  (i)  by 
continuity  and  contiguity  of  the  tissues  (per  contimdtatem,  per 
contiguitafem) ,  (2)  by  the  blood  or  lymphatic  tissues  {hcematogen- 
oi!S,  lymphogenous),  and  (3)  as  already  referred  to,  the  func- 
tional interdependence  of  one  organ  upon  the  others  may,  in  case 
of  disease  at  one  point,  lead  to  further  change  in  other  parts  of  the 


Extension   uf  Disease;    Termimition   of  Disease.  99 

system   {sympathetic  or  consecutive  lesions).     By  the  term  exten- 
sion  by  continuity  is  understood  the  progress  of  the  pathological 
process  upon  the  surfaces  in  continuity  and  along  uninterrupted 
tissues  in  the  immediate  vicinity  of  the  original   focus,   as   along 
the  mucous  membrane  of  the  nose  to  the   frontal   and  maxillary 
sinuses,   from   the   pharynx  to   the    Eustachian   tubes   and   middle 
ears.     Extension  by  contigxiity  occurs  from  one  surface  to  that  of 
an  adjacent  organ  in  contact  with  the  first,  as  from  the.  visceral 
pleura  to  the  costal  pleura,  from  the  serous  surface  of  the  stomach 
to  the  liver.     The  explanation   for   such   a   mode   of  extension  is 
mainly  to  be   found   in  the   fact  that   the   pathogenic   agent  finds 
some   particular  opportunity   for   invading   such   adjacent   tissues; 
thus  bacteria  may  pass  to  an  adjoining  structure,  be  swept  along 
by   its   fluids   and   spread   widely.      A   suppurative   or   gangrenous 
focus   in  the  lung  may  in  some  such   manner  gain  access  to  the 
pleura;   the   latter   may   rupture   and   the   microorganisms,    spread 
over  the   entire   pleural   surface   from  the   respiratory  movements, 
mav  give  rise  to  an  extensive  pleuritis.     Hccmatogenous  extension 
of  a  disease  occurs  when  the  pathogenic  agents  gain  access  to  the 
blood;    IxmpJwgcnous    cxtcnsioji.    when    such    influences,    through 
the  agency  of  the   wandering  cells,   are   mingled   with  the  lymph 
(cf.  emboHsm).     Sympathetic  disturbances  in  function  arc  appar- 
entlv   in    part   the   result   of   sensory   and   motor   reflex   action,    in 
part   the   result   of   primary   changes,   the  etficiency   of   one   organ 
depending  upon  the  functional  integrity  of  another,  as  a  chronic 
hepatic  cirrhosis  induces  cardiac  hypertrophy  and  splenic  cyanosis 
by  the  circulatory  disturbances  which  it  produces. 

Coincidence  of  diseases  may  occur  entirely  independently  of  any 
relation  between  the  processes,  or  may  depend  upon  some  connec- 
tion;  where  this  occurs  complications  are  said  to  exist.  Thus 
swine-erysipelas  is  often  complicated  by  valvular  endocarditis  (the 
infectious  germs  invading  the  latter  structures),  o'-  suppurative 
osteitis  of  the  cranium  may  be  complicated  by  a  meningitis 
(through  extension  of  the  suppuration  by  contiguity  to  the 
meninges). 

The  termination  of  disease  may  result  in  one  of  three  ways: 

1.  Recovery,  cure  or  restoration,  complete  re-establishment 
of  the  disturbed  function  and  condition  of  the  organ ; 

2.  Incomplete  recovery,  with  appearance  of  secondary  affec- 
tions, persistence  of  sequels  or  defects ;  or 

3.  Death  of  the  individual. 


lOO  Termination  of  Disease. 

Tcnniiiation  in  recovery  is  accomplished  through  the  repara- 
tive powers  natural  to  the  economy.  The  body  is  possessed  of  a 
variety  of  regulative  mechanisms,  whereby  the  influence  of  harm- 
ful agencies  is  neutralized,  the  loss  of  chemical  substances  and 
tissues  is  repaired,  and  noxious  materials  are  eliminated  from  the 
system.  Such  processes  may  in  a  compensatory  fashion  correct 
this  or  that  fault,  as  by  the  discharge  of  toxic  matter  from  the 
stomach  or  intestines,  the  removal  of  the  products  of  fatigue  from 
the  muscles  and  nerves  through  the  blood  and  lymph,  the  expul- 
sion of  exudations  from  the  lungs  through  expectoration.  IVIany 
corpuscular  disturbing  factors  (as  bacteria,  dead  cells,  haemor- 
rhagic  foci)  are  removed  through  the  activity  of  the  living  cells 
(phagocytes)  and  digested,  the  body  being  thus  freed  of  such  sub- 
stances. Other  foreign  bodies  are  encapsulated  by  a  wall  formed 
by  the  tissues  of  the  organism  for  their  own  protection,  and  thus 
rendered  harmless.  Deficiency  of  nutritive  material  in  the  fluids 
and  cells  is  corrected  by  the  supply  from  the  stomach  and  intes- 
tine ;  dead  cells  are  replaced  by  new  elements  from  existing  forma- 
tive areas  (as  new  blood  cells  from  the  bone-marrow).  Tissue 
losses  are  repaired  by  processes  of  regeneration.  And,  too,  the 
production  of  antibodies  of  most  varied  type  is  possible  for  the 
protection  of  the  animal  body. 

The  therapeutic  art  is  in  no  wise  at  variance  with  natural  proc- 
esses of  recovery,  but,  on  the  contrary,  employs  the  various  regu- 
lating and  compensatory  mechanisms  of  the  body  in  order  to  bring 
about  an  adjustment  of  the  disturbances,  and  attempts  to  induce 
conditions  more  favorable  to  a  rapid  adjustment  than  is  possible 
when  no  influence  is  brought  to  bear  upon  the  pathogenic  agent ; 
at  the  same  time  it  attempts  to  restrain  further  agencies  which 
may  retard  the  recovery.  The  practice  of  medicine  is  also 
directed  to  guard  against  the  extension  of  contagious  diseases  and 
particularly  against  the  inception  of  disease,  so  that  in  this  phase, 
too,  the  lofty  power  of  science  holds  nature  in  check,  which,  with- 
out the  aid  and  skilled  intervention  of  man.  would  threaten  with 
annihilation,  all  too  soon,  the  creatures  of  the  earth.  The  sienifi- 
cance  and  success  of  medical  science  is  particularly  impressed 
upon  one  when  it  is  recalled  how  destructive  epidemic  diseases, 
which  in  times  past  carried  ofif  millions  of  animals  and  men,  have 
in  some  instances  been  wholly  eradicated,  in  other  instances  greatlv 
diminished.  By  appreciation  of  the  nature  of  a  varied  group  of 
affections,  there  has  come  the  discovery  of  efficient  methods   for 


Tcriniiialidii  iii  Recovery:    Pcalli.  loi 

their  cure  and  for  proph>laxis  against  them.  Of  course,  no  rem- 
edy has  been  found  for  death,  the  inevitable  end  of  development 
of' all  living  beings,  and  the  laws  of  nature  can  by  no  medica- 
ment, whatever  its  power,  be  broken.  Yet  the  skillful  use  of  the 
means  of  nature  may  hold  ofif  premature  death  and  may  assist  the 
injured  body  to  regain  its  health.  Medical  art  can  prevent  fatal 
haemorrhages,  it  loosens  adhesions,  cuts  away  what  is  unfit, 
dilates  narrow  canals,  has  antidotes  at  its  disposal,  can  procure 
rapid  evacuation  of  the  bowel  or  emesis,  remove  foreign  objects 
from  the  body,  relieve  promptly  nervous  strain,  alleviate  pain 
directly,  often  correct  irregularity  of  cardiac  action,  reduce  dan- 
gerous temperatures  and  accomplish  a  multitude  of  services  with- 
out which  a  given  disease  might  well  end  unfavorably  or  be 
protracted  over  a  tedious  course. 

After  recovery  begins  at  the  close  of  a  general  affection,  there 
occurs  a  period,  known  as  convalescence,  the  subject  still  evincing 
muscular  weakness  and  marked  sensitiveness  to  external  influences. 
[During  this  period  there  are  taking  place  various  reparative  and 
reconstructive  processes  in  the  economy,  looking  to  the  restoration 
of  altered  and  destroyed  elements,  and,  too,  functional  efficiency  is 
being  re-established,  and  all  remaining  factors  of  the  previous 
disease  are  being  finally  eliminated  from  the  system.] 

Recovery  is  regarded  as  incomplete  where,  after  a  disease  has 
run  its  course,  there  persist  in  the  economy  conditions  preventing 
normal  functional  efficiency  of  the  organs  or  where  there  is  evi- 
dent some  permanent  impairment  of  tissue  [sequelcc  of  disease]. 
As  illustrative  of  this  may  be  mentioned  deformities  of  bones, 
cicatricial  strictures  of  canals,  kinks  of  the  intestines,  pericardial, 
pleural  or  other  adhesions  by  bands  of  connective  tissue  result- 
ing from  the  previous  disease,  opacity  of  the  normally  transparent 
media  of  the  eye,  palsies  of  muscles  and  nerves,  or  the  defects 
left  after  ulceration  or  burns. 

Termination  of  disease  in  death  (e.vitiis  lethalis  or  letalis, 
from /t^f7/;;/,  death;  from  Ky)et)  forgetfulness,  \avedvw  to  make  forget- 
ful) occurs  when  the  organs  which  subserve  the  most  important 
and  necessary  processes  of  vitality  suspend  their  function.  Inas- 
much as  continuance  of  life  depends  in  an  important  measure 
upon  the  uninterrupted  supply  of  blood  containing  oxygen  to  the 
medulla  oblongata  through  the  action  of  the  heart,  underlying  which 
must  be  recognized  the  necessity  for  respiratory  movements  regu- 
lating the   efficiency   of  the   pulmonary   surface    in   the   intake   of 


102  Termination  of  Disease. 

oxygen  and  output  of  carbon  dioxide,  it  is  essential  to  accept  as 
causes  of  death  of  primary  importance,  various  lesions  and  func- 
tional disturbances  of  the  hind  brain,  the  heart  and  the  lungs. 
These  parts  are  therefore  spoken  of  as  the  atria  mortis.  Inhibi- 
tion of  their  functions  may  be  a  direct  result  of  chemical,  me- 
chanical or  electrical  influences  (as  from  poisons  which  destroy 
or  paralyze  the  nerve  cells,  concussion,  the  action  of  lightening), 
or  may  indirectly  follow  a  wide  variety  of  factors  interfering 
with  tissue  nutrition,  metabolism  and  gaseous  interchange  (anse- 
mia,  albuminous  waste,  closure  of  respiratory  passages,  elevation 
or  depression  of  body-temperature,  reflex  palsies).  The  more 
important  modes,  therefore,  by  which  this  or  that  disease  may 
induce  death,  are : 

1.  Cessation  of  cardiac  action,  caused  by  toxic  or  reflex  nerv- 
ous paralysis  of  the  cardiac  ganglia,  fatigue  and  degeneration  of 
the  cardiac  muscle,  cardiac  rupture,  complete  obstruction  to  the 
escape  of  blood  from  the  cardiac  chambers  (formerly  known  as 
e.ritus  lethalis  per  syncopeni,   (tw-koitthv,  to  strike  together). 

2.  Asphyxiation,  from  interference  with  intrapulmonary 
respiratory  interchange  of  gases,  obstruction  of  the  lungs  or  upper 
respiratory  passages,  compression  of  these  tubes,  spasm  or  palsy 
of  the  respiratory  muscles,  diaphragmatic  rupture  (exitus  lethalis 
per  suffocationem). 

3.  Mednllary  Paralysis,  or  paralysis  of  the  respiratory  centre 
in  the  medulla  oblongata,  from  circulatory  interference  at  the 
base  of  the  brain,  influence  of  toxic  substances  upon  the  nerve 
cells,  concussion  of  the  brain  or  reflex  influences  (exitns  lethalis 
per  apoplexiain,  d-n-owXricraei.i',  to  strike  down). 

4.  Hceniorrhage,  from  rupture  of  important  vessels,  or  ex- 
travasation of  large  amounts  of  blood  into  the  somatic  and 
visceral  cavities. 

5.  Exhaustion,  from  inanition  or  consumption  (diminished 
nutrition  and  exaggerated  metabolism,  accumulation  of  fatigue 
products  and  poisonous  metabolites,  auto-intoxication). 

These  modes  of  death  may,  of  course,  complicate  each  other 
and  may  be  mutually  causative  of  each  other  (as  when  haemor- 
rhage induces  ischsemia  of  the  heart  and  coronary  vessels,  with 
the  result  of  cardiac  cessation  and  at  the  same  time  the  symptoms 
of  suffocation,  due  to  an  anaemia  of  the  medulla).  Senile  debility, 
more  or  less  complicated  by  various  diseases,  is  also  to  be  re- 
garded as  a  cause  of  death    (senile  marasmus,   from   ^apaiveiv,  to 


Tcniiiiiatioii   in  Death.  103 

weaken),  a  natural  and  necessary  termination  for  each  individual 
cell  and  for  the  entire  cellular  complex.  In  the  individual  cell,  as 
well  as  in  all  the  tissues  of  the  organism  of  higher  animals, 
changes  are  continually  proceeding  which  lead  to  the  destruction 
of  the  living  substance  and  sooner  or  later  result  in  the  death  of 
the  individual.  The  living  multinucleated  organism  is  continually 
losing  cells  by  their  death,  the  substance  of  which  is  eliminated 
from  the  economy  with  the  excretory  material  or  is  broken  up  and 
re-employed  by  the  system.  From  causes  inherent  in  the  organ- 
ism itself,  but  at  present  impossible  of  clear  definition  (vid.  Ver- 
worn:  Geschichte  des  Todes ;  Allgem.  Physiologic)  the  power  of 
multiplication  ceases  in  the  individual  groups  of  cells  and  organs 
in  varying  rates  in  the  different  species  of  animals,  and  with  vary- 
ing swiftness  the  characteristics  of  old  age  and  of  death  become 
apparent.  Perpetual  youth,  immortality  in  the  sense  of  reproduc- 
tion, always  renewing  themselves,  is  possible  only  for  the  conju- 
gated sexual  cells  (propagation  cells),  while  in  case  of  the  somatic 
elements  (and  those  sexual  cells  failing  of  copulation)  the  vegetal 
force  sooner  or  later  disappears.  Whenever  the  decay  of  cells  of 
vital  importance  reaches  the  grade  in  which  it  distinctly  interferes 
with  the  rest  of  the  economy,  the  mutual  relations  of  the  various 
parts  is  disturbed,  and  death  ensues,  just  as  a  clock  stops  when 
its  wheels  wear  out  or  are  broken. 

Transition  from  life  to  death  may  occur  suddenly  (mors  subi- 
tanea) ;  the  animal  falls  from  its  standing  position  to  the  ground, 
becomes  unconscious,  and  for  a  few  moments  at  most  is  thrown 
into  convulsions  with  groaning  respirations.  Such  sudden  termi- 
nation may  be  noted  in  death  from  lightening  stroke,  sun  stroke, 
rupture  of  the  heart,  cerebral  concussion,  massive  internal  haemor- 
rhages or  cardiac  and  cerebral  paralysis.  In  the  majority  of  in- 
stances, however,  death  comes  on  gradually,  with  the  manifesta- 
tion of  characteristic  phenomena  w'hich'  predict  the  termination  of 
life,  and  which  together  constitute  what  is  knowm  as  the  death- 
agony  (t7  ayuvla,  the  Struggle,  death  struggle).  They  include  the 
signs  of  a  progressive  paralysis  of  the  nervous  and  muscular  sys- 
tems, together  with  those  of  the  disease  which  causes  death. 
Animals  in  the  agonal  state  are  unable  to  raise  themselves  from 
the  ground,  usually  lie  flat  on  one  side,  from  time  to  time  lifting 
the  head  and  letting  it  fall  heavily  to  the  ground,  with  the  feet 
rigidly  extended  and  moved  convulsively,  at  first  violently,  but 
gradually    more    and    more    weakly.      Respiration    is    slowed    and 


104  Termination  of  Disease. 

labored,  deep  groaning-  respirations  following  at  irregular  inter- 
vals the  ordinary  shallow  breathing.  With  the  appearance  of  pul- 
monary oedema,  rales,  heard  even  at  a  distance,  are  produced  by 
the  fluid  exudate  beaten  into  a  foam  in  the  air  passages  (death 
rattle).  Involuntary  discharges  occur  from  the  bowel  and  blad- 
der, when  paralysis  of  the  sphincter  muscles  develops.  The  heart 
beats  more  rapidly,  but  the  relaxed  arteries  are  no  longer  able  to 
propel  the  blood  forward  and  the  pulse  in  consequence,  although 
quick,  grows  small  and  finally  indistinguishable,  and  the  skin  i? 
cool.  The  hair  is  bathed  with  a  clammy  sweat.  The  body  tem- 
perature in  the  agonal  period  in  diseases  accompanied  by  loss  of 
blood  or  inanition  falls  considerably  below  normal  (hypothermia, 
to  36-35°  C),  while  in  other  types  there  may  be  an  ante- 
mortem  rise  in  temperature.  Extinction  of  life  means  complete 
cessation  of  metabolism,  of  cellular  growth  and  the  existence  of 
the  individual ;  and  death  therefore  manifests  itself  by  complete 
termination  of  the  functions  of  all  parts  of  the  body.  The  last 
breath,  naturally  in  the  form  of  expiration,  and  the  moment  of 
complete  cessation  of  the  heart  may  ordinarily  be  looked  upon  as 
marking  the  actual  end  of  life.  However,  the  organs  do  not  all 
perish  at  precisely  the  same  moment;  after  the  last  breath  the 
heart  may  flutter  a  few  minutes ;  and  after  death  from  haemorrhage, 
peristaltic  movements  of  the  intestines  may  sometimes  be  ob- 
served for  perhaps  fifteen  minutes ;  and  similarly  after  death  from 
electricity  muscular  contractions  may  be  elicited  as  long  as  rigor 
mortis  does  not  set  in  (one  to  three  hours  after  death). 

The  following  are  the  characteristic  signs  of  true  somatic 
death : 

1.  Muscular  rigidity  {rigor  mortis),  sometimes  setting  in  im- 
mediately after  death,  sometimes  only  after  four  to  twenty  hours 
later,  and  depending  upon  the  coagulation  of  the  muscle  albumen. 
The  muscles  in  this  change  become  set,  shortened  and  thickened,  as 
in  vital  contractions ;  the  extremities  are  rigid  and  either  cannot 
be  flexed  or  only  with  the  application  of  considerable  force,  and 
the  mouth  cannot  be  opened  by  ordinary  traction  upon  the  lower 
jaw.  After  twenty-four  hours,  or  perhaps  later,  the  rigidity 
disappears   [due  to  decomposition]. 

2.  Cadaveric  fall  of  temperature  (algor  mortis)  develops  in 
from  half  an  hour  to  twenty-four  hours  after  death,  varying  with 
the  surrounding  temperature  and  the  degree  of  metabolic  activity 
prevailing  at  the  time  of  the  death  agony.  In  some  affections,  as 
in  tetanus,  because  of  the  important  heat  production  caused  by  the 


Signs  of  Death.  105 

muscular  contractions  and  because  after  death  heat  dissipation 
falls  on  account  of  the  cessation  of  the  circulation  in  the  peri- 
phery of  the  body,  a  post-lethal  internal  temperature  rise,  to 
perhaps  42-44°  C,  occurs,  persisting  a  number  of  hours. 

3.  The  eye  in  death:  The  eyelids  of  the  cadaver  are  usually 
half  open  (rigidly)  ;  the  ocular  bulb  is  sunken  and  somewhat  less 
tense  than  in  life  (evaporation  of  some  of  its  fluids)  ;  the  cornea 
becomes  dull  and  opaque ;  the  pupils  are  dilated.  The  ocular  reflex 
movements   upon   touch   are  entirely   absent. 

4.  Appearance  of  putrefaction:  The  bacteria  in  the  digestive 
tract,  producing  all  sorts  of  fermentative  changes  in  the  contents 
of  the  canal,  shortly  after  the  death  of  the  tissues,  penetrate  the 
latter  and  cause  their  putrefaction.  The  gases,  produced  in  large 
quantities  from  the  fermentative  processes,  dilate  the  stomach  and 
intestines,  causing  abdominal  distension,  sometimes  to  such  a 
degree  as  to  force  the  lower  bowel  out  of  the  anus,  rupture  the 
diaphragm  and  allow  the  intruding  intestines  to  distend  the  chest. 
The  advance  of  putrefaction  may  be  noted  in  the  colorless  parts 
of  the  skin  by  greenish  discolorations  (sulphur  compounds  of 
haemoglobin),  and  also  by  the  foul  odors  of  cadaveric  decomposi- 
tion. These  changes  cause  the  disappearance  of  the  rigidity  of 
the  body  and  progress  the  more  rapidly  the  warmer  the  surround- 
ing temperature.  Measures  which  inhibit  the  growth  of  the 
putrefactive  bacteria,  preservation  in  alcohol  or  formaline  (injection 
of  the  vessels  with  antiseptic  or  balsamic  substances),  refrigera- 
tion, drying,  prevent  putrefaction.  With  the  advance  of  putre- 
faction all  the  organic  matter  of  the  body  is  broken  up  into 
ammoniacal  compounds,  carbonic  acid  and  water,  with  the  forma- 
tion of  a  great  variety  of  by-products  (putrefactive  alkaloids, 
acids,  gas-forming  matter,  etc.)  until  finally  only  the  solid  calcified 
bones   remain. 

The  name  apparent  death  is  applied  to  a  condition  in  which  all 
the  vital  functions  are  depressed  to  the  ^owest  possible  degree, 
when  only  by  great  care  in  the  examination  of  the  seemingly  dead 
body  can  there  be  detected  feeble  cardiac  contractions  and  occa- 
sional faint  respiratory  movements,  a  condition  accompanied  by  loss 
of  consciousness  and  sensibility,  and  by  reduction  of  the  body 
temperature.  In  recently  born  animals  this  condition  is  seen  com- 
paratively frequently,  lasting  perhaps  for  hours  (asphyxia  neona- 
torum) ;  in  this  connection  it  is  perhaps  due  to  a  premature  separa- 
tion of  the  placenta,  aspiration  of  the  amniotic  fluid,  compression 
of  the  umbilical  cord,  or  to  anaemia. 


DISTURBANCES    OF   CIRCULATION 

Life  and  health  are  possible  for  the  organs  only  if  there  be 
unimpaired  circulation  of  a  blood  capable  of  supplying  oxygen 
and  nutrition  to  them.  Disturbances  of  the  circulation,  as  well  as 
faults  of  the  blood  and  lymph,  in  other  words,  deficiency  in  the 
provision  and  passage  of  good  blood  through  the  organs,  endanger 
both  life  and  health. 

The  normal  heart  possesses  a  notable  adaptabilty  to  the  varying 
demands  upon  its  capacity  for  work ;  it  accommodates  itself  im- 
mediately to  the  current  of  blood  entering  it  by  virtue  of  the  elas- 
ticity of  its  walls ;  regulates  the  energy  and  rhythm  of  its  contrac- 
tions in  conformity  to  the  amount  of  blood  in  its  chambers,  the 
general  circulatory  resistance  and  the  demand  for  blood  in  the  ac- 
tive or  resting  organs.  This  power  of  accommodation  enables  it,  to 
a  certain  extent,  to  overcome  and  compensate  for  pathological  dis- 
turbances affecting  the  hasmic  circulation ;  under  such  circumstances 
there  is  said  to  take  place  a  compensation  for  these  disturbances. 

Where  such  conditions  of  resistance  to  the  heart's  action  are 
of  slow  development  and  permanent,  a  thickening  of  the  myocar- 
dium is  assumed  in  connection  with  the  increased  requirement  for 
work,  consisting  essentially  in  an  increase  in  the  number  and  size 
of  the  muscular  elements  (cardiac  hypertrophy).  It  may  be 
said  that  even  physiologically  the  size  and  muscular  strength  of  the 
heart  are  adjustable  to  the  demands  made  upon  it  in  its  function 
as  a  forcing-pump  or  as  a  suction  pump.  Certain  animals,  for 
example,  which  in  the  course  of  their  lives  perform  especially 
intense  muscular  work,  are  likely  to  exhibit  hearts  larger  in  pro- 
portion to  the  body-weight  than  animals  accustomed  to  but  little 
muscular  activity."*-  Pathological  hypertrophy  differs  from  this 
physiological  form  only  in  its  cause,  in  the  latter  the  excessive 
work  being  but  a  natural  and  customary  condition  in  the  life  of  the 
animal,   in  the   former  the   result   of  abnormalitv   of  the   vascular 


►See  also   Kitt,   Lehrbuch   der  patliol.  Anatomic   d.     Haustiere.     II.    Aufl. 


Cardiac  Hypertrophy.  107 

system,  of  excessive  blood  pressure  and  of  unusual  quantities 
of  blood  within  the  organ.  Such  'Svork-hypertrophy"  of  the  gen- 
eral organ  is  met  in  connection  with  epicardial  adhesion  to  the 
parietal  pericardium,  compression  of  the  base  of  the  heart  from 
pleuritic  adhesion,  tumors  or  similar  conditions,  because  in  such 
cases  the  propulsive  effort  of  the  entire  organ  has  a  greater  oppo- 
sition to  overcome. 

Hypertrophy  of  one  side  of  the  heart  is  seen  especially  in  case 
of  valvular  lesions.  These  valvular  lesions  involve  irregularities 
in  the  closure  of  the  orifices  of  the  heart  and  its  great  vessels  ; 
they  are  of  two  types,  either  narrowing  of  the  orifices  from  pro- 
liferative changes,  bloods  clots,  etc.  (stenosis),  or  incompleteness 
of  closure  of  the  orifices  by  the  valves  {valvular  insufficiency). 
Stenosis  at  the  aortic  opening  increases  the  work  of  the  left  ven- 
tricle in  order  that  the  blood  may  be  forced  through  the  narrowed 
orifice,  and  in  proportion  there  ensues  a  work-hypertrophy  of  the 
left  ventricular  wall.  Following  stenosis  at  the  origin  of  the  pul- 
monary artery  there  occurs  a  work-hypertrophy  of  the  right  heart 
(sometimes  dilatation  after  special  preceding  strain).  X'alvular 
insufficiency  also  leads  to  hypertrophy,  because  where  the  valves 
are  incompletely  closed  there  first  occurs  a  tendency  to  stasis 
because  of  the  back  pressure  of  the  blood  (regurgitation),  which  is 
likely  to  induce  ventricular  or  auricular  dilatation,  and  therefore 
the  heart  is  required  to  work  the  harder  in  order  to  propel  the  larger 
quantity  of  blood.  Although  the  so-called  compensatory  hyper- 
trophy of  the  heart  does  in  some  measure  contribute  to  the  regula- 
tion of  the  blood  distribution  and  is  of  some  service,  yet  in  reality 
it  is  only  the  expression  of  an  increased  blood-pressure  in  one  of 
the  ventricles  or  auricles  or  in  the  aft'erent  or  efferent  vessels,  and 
the  compensation  which  it  induces  is  only  a  relative  one.  As  a 
matter  of  fact,  the  increase  of  pressure  persists  and  the  circulation 
does  not  become  normal  (Krehl).  Even  when  the  animal  is 
at  rest  the  continued  heightened  blood  pressure  causes  the  develop- 
ment of  dilatation  of  the  capillaries,  pulmonary  passive  congestion 
and  distension  with  consequent  diminution  in  the  pulmonary  excur- 
sion, together  with  difficulty  in  breathing.  The  arteries  show  dis- 
tinct changes  of  the  pulse,  the  vessels  being  unusually  tense  and 
distended ;  they  eventually  lose  their  elasticity  and  may  rupture. 
A  very  large  heart  may  in  addition  mechanically  interfere  with 
the  lungs.  These  consequences  are  still  more  evident  if  the  indi- 
vidual exercises  physically,  the  muscular  exertion  raising  the  blood 


io8  Disturbances  of  Circulation. 

pressure  still  higher.  (Powerful  muscular  contractious  force 
larger  amounts  of  blood  into  the  right  heart ;  the  ventricles  become 
engorged  and  the  hsemic  pressure  rises.)  Eventually  the  heart 
loses  its  force  as  a  pathological  hypertrophy  is  not,  as  might  be  sup- 
posed from  the  thickness  of  the  walls,  capable  of  indefinite  response 
to  increased  functional  demands,  but  on  the  contrary,  is  often 
unable  to  accomplish  even  the  more  moderate  requirements  made 
upon  the  strength  of  the  heart.  Perhaps  the  reason  for  this  is  that  the 
influences  which  give  rise  to  cardiac  hypertrophy  at  the  same  time 
harm  the  myocardium  in  other  respects.  For  example,  valvular 
lesions,  causing  the  heart  to  become  hj'pertrophied  in  their  train," 
are  frequently  caused  by  infectious  substances.  Such  agencies  may 
also  cause  a  myocarditis;  and  if  the  inflammation  be  protracted  and 
of  low  grade,  it  causes  considerable  reduction  in  the  efficiency  of 
the  muscle.  Moreover,  the  conditions  which  cause  pathological 
cardiac  hypertrophy  are  typically  not  stationary,  but  on  the  con- 
trary the  circulatory  difficulties  are  apt  to  progress  (the  stenosed 
orifices  are  likely  to  become  still  more  narrowed,  thrombi  which 
interfere  with  the  vascular  lumen  become  larger,  capillary  areas 
become  contracted)  ;  and  from  such  extra  demands  upon  its  ability 
the  heart  becomes  fatigued.  There  must  eventually,  therefore,  suc- 
ceed upon  compensatory  hypertrophy  a  period  of  failure  of  com- 
pensation, a  period  of  broken  compensation.  [There  are  numer- 
ous influences  which  combine  to  limit  cardiac  hypertrophy*  and  to 
determine  its  eventual  loss  of  compensatory  power,  and  so  certain 
and  uniform  are  these  results  that  it  might  well  be  declared  a  law 
that  every  pathological  hypertrophy  of  the  heart  must  necessarily 
reach  a  limit  to  its  enlargement  and  must  thereafter  fail  in  its  power 
of  compensation  and  undergo  degenerative  changes.  The  limita- 
tions, aside  from  those  set  by  the  age  of  the  muscle  and  its  inher- 
ent power  of  increase,  depend  mainly  upon  the  amount  of  proper 
blood  which  the  coronary  vessels  are  able  to  supply.  In  a 
great  measure  this  is  determined  by  the  original  size  and  construc- 
tion of  these  vessels,  although  doubtless  there  is  a  possibility  of 
true  hypertrophy  in  these  so  as  to  accommodate  the  growing  needs 
of  the  enlarging  organ ;  yet  if  the  original  cause  of  the  hypertrophy 
were  a  widespread  arteriosclerosis  the  coronary  arteries  would 
be  extremely  likely  to  have  been  involved.  Even  were  this  not 
true,  the  mechanical  influence  of  a  hypertrophied  left  ventricle 
upon  the  walls  of  these  vessels  in  close  functional  and  topograph- 
ical relation  with  the  pumping  action,   and  the  similar  influences 


Cardiac  failure.  109 

of  tlie  aortic  recoil  after  closure  of  the  aortic  valve,  must  favor 
the  development  of  a  local  coronary  sclerosis  on  account  of  the 
possibility  of  fibrillary  injuries  to  the  walls.  Given  an  arterio- 
sclerosis there  is  every  reason  to  expect  an  imperfection  of  the  cor- 
onary circulation  from  the  narrowin";  of  the  lumen  and  the  in- 
creased rigidity  of  the  tubes  ;  and  with  the  imperfection  of  circu- 
lation thus  fixed  upon  the  myocardium,  its  nutrition  and  ability 
to  further  enlarge  are  necessarily  limited.  The  functional  de- 
mands progressing,  fatigue,  degeneration  and  cardiac  failure  are 
the  necessities  of  a  not  distant  future.] 

Diminution  of  cardiac  force  is  spoken  of  as  cardiac  failure, 
cardiac  iiisutficioicy.  It  follows  various  influences  afl'ecting  the 
myocardium  or  its  ganglia,  among  wdiich  as  prominent  examples 
mav  be  mentioned  excessive  exertion  or  fatigue,  numerous  poisons 
and  the  analogous  substances  present  in  the  system  in  the  infectious 
diseases,  diminution  in  the  blood  supply  to  the  myocardium,  in- 
flammations and  degenerations  of  the.  muscle,  excessive  fatty  de- 
posits of  the  heart,  and  atroi-)hy  of  the  myocardium.  All  patholog- 
ical changes  which  occasion  cardiac  insufiiciency  are  followed  by 
disturbances  in  the  movement  and  distribution  of  the  blood.  A 
fatigued  and  weakened  heart  is  incapable  of  normal  contraction, 
expels  from  its  chambers  a  smaller  amount  of  blood  than  normally ; 
in  consequence  the  arteries  are  not  properly  filled,  the  blood  press- 
ure sinks  in  them  and  the  movement  of  the  current  is  slowed.  The 
aspirating  power  of  a  weak  heart  is  also  low  and  the  blood  moves 
less  freely  from  the  venous  side  of  the  circulation,  the  veins  becom- 
ing engorged  and  the  pressure  raised.  The  results  of  these  irregu- 
larities differ  somewhat  as  the  left  or  right  heart  alone  or  the 
whole  organ  is  especially  involved ;  in  one  case  the  lesser  circula- 
tion, in  the  other  the  greater  being  the  more  disturbed.  Many 
variations,  too,  are  occasioned  by  the  grade  of  cardiac  insufficiency 
and  by  the  nature  of  the  original  causes  (cf.  ancvmia  and  hypcr- 
(DJua).  The  luyocardium  being  weak  the  cardiac  cavities  do  not 
contract  as  in  normal  conditions,  contain  an  excess  of  blood,  and 
this  engorgement  gives  occasion  for  dilatation  of  one  or  both  sides 
of  the  organ. 

Left  ventricular  insufficiency  determines  imperfect  filling  of  the  aorta 
and  its  branches,  and  in  consequence  deficiency  in  the  amount  of  arterial' 
blood  going  to  the  brain,  skin,  glands  and  elsewhere.  The  heart,  however, 
remains  full  and  the  blood  is  dammed  back  into  the  pulmonary  veins,  and 
the  right  heart  experiences  marked  difficulty  in  forcing  the  blood  through 
the  lungs.     Insufficience  of  the   right   heart,   on  the   contrary,   causes   incqm;^ 


no  Disturbances  of  Circulation. 

plete  filling  of  the  pulmonary  artery,  pulmonary  anaemia,  and,  of  course,  the 
left  heart  in  its  turn  receives  unduly  low  amounts  of  blood.  In  the  right 
auricle  and  larger  veins  engorgement  ?.nd  tension  become  marked,  tending 
to  cause  a  passive  engorgement  of  the  venous  system  throughout  the  body, 
a  cyanotic  liver,  cyanotic   spleen,   etc. 

A  heart  reduced  in  its  propulsive  power  is  itself  but  poorly 
supplied  with  blood  because  its  own  arteries  are  but  incompletely 
supplied.  Any  condition  of  fatigue  which  prevails  may  there- 
fore easily  become  c.vhaiistion,  complete  functional  inability,  arrest 
of  cardiac  action  ( cardiac  paralysis,  cardiac  syncope,  cardiac  col- 
lapse). All  these  terminal  changes  interfering  with  circulatory 
integrity  are  occasioned  by  any  influences  which  impair  the  con- 
tractile efficiency  of  the  myocardium,  any  agencies  which  either 
directly  or  indirectly  reduce  its  muscular  power  (rupture,  fatty 
degeneration,  inflammation,  prevention  of  expansion  of  the  heart 
from  some  external  interference,  anaemia)  ;  in  the  same  way  the 
action  of  some  paralyzant  toxine  upon  the  cardiac  ganglia,  the 
analogous  action  of  thermic  and  electric  agencies,  excessive  reflex 
stimulation  of  the  vagus  or  of  the  vagus  nucleus  in  the  medulla 
oblongata  (the  latter  from  deficiency  of  the  blood  oxygen, 
increased  blood  pressure  in  the  brain,  or  toxines). 

Just  as  in  cases  of  diseases  of  the  heart,  affections  of  the 
arteries  and  veins  are  apt  to  occasion  irregularity  of  distribution 
and  movement  of  the  blood  in  given  organs  and  areas  of  the 
body.  Narrow'ing  of  the  arteries  from  vasoconstriction  (arterial 
spasm),  thrombus  formation,  inflammation  and  permanent  shrink- 
age raise  the  intracardiac  blood  pressure  and  occasion  dilata- 
tion and  hypertrophy ;  the  organ  to  which  such  a  constricted 
artery  is  distributed  is  imperfectly  supplied  wath  blood  and  a 
variety  of  changes  may  in  consequence  occur  in  it  (cf.  ancrniia 
and  embolism).  Decrease  in  the  elasticity  of  the  vascular  walls 
or  paralysis  of  the  arterial  musculature  permits  the  vessels  to 
dilate,  the  current  to  become  slowed  and  the  organ,  congested. 
Reduction  in  the  muscular  jionus  of  the  vessels  of  the  splanchnic 
area  from  vasomotor  paralysis,  usually  from  toxic  and  infectious 
influences,  causes  a  massive  congestion  of  the  abdominal  vessels ; 
in  consecjuence  of  which  the  general-  blood  pressure  falls,  cardiac 
labor  from  the  small  amount  of  blood  coming  to  the  organ  ensues, 
and  there  is  a  fatal  collapse   (Krehl). 

In  the  veins  interference  with  the  progression  is  occasioned 
not   only   by   cardiac   weakness,   cardiac     lesions    and    pulmonary 


Hypcrcctuia  ami  Anccmia.  iii 

affections  which  interfere  with  the  aspiration  factor  of  venous  cir- 
culation and  h\-  thromhosis  of  the  veins  ;  but  it  should  also  be  kept 
in  mind  that  any  abnormal  compression  of  these  thin-walled  veins 
must  interfere  with  the  return  flow  of  blood.  The  nearer  the 
heart  such  compression  occurs  the  greater  the  harm  to  the  gen- 
eral body.  Compression  of  the  two  venae  cavre,  which  from  the 
compressibility  of  these  vessels  is  quite  possible  from  pleural  effu- 
sions, induce  a  reduction  in  the  amount  of  blood  entering  the 
cardiac  chambers  and  venous  congestion  throughout  the  economy 
(cf.  hyperconiia). 

The  lymph  supply  and  drainage  are  in  close  relation 
with  the  abnormalities  of  the  blood  vascular  system  and  blood 
circulation ;  imperfections  in  the  lymphatic  circulation  give  rise  to 
abnormal  accumulations  of  fluid  in  the  lymph  vessels  and  serous 
cavities  and  occasion  a  wide  group  of  organic  lesions. 

Local  Variations  in  Amount  of  Blood.     Hyperaemia  and  Anaemia. 

The  amount  of  blood  in  the  organs  of  even  healthy  individuals 
is  always  subject  to  change  and  variation.  The  vessels  are  elastic 
tubes  which  are  expanded  by  greater  internal  blood  pressure  and 
adjust  themselves  as  their  contents  diminish.  This  is  not  merely 
a  passive  accommodation,  however ;  they  are  capable  of  active 
contraction  and  dilatation  through  the  power  of  the  smooth  muscle 
in  their  structure,  such  alterations  of  lumen  being  primarily  under 
control  of  nervous  influences.  The  total  quantity  of  blood  in 
the  body,  similarly  subject  to  continual  variation,  is  never  so  great 
as  to  completely  fill  all  the  vessels  were  they  fully  dilated ;  there 
exists,  however,  a  moderate  fullness,  varying  here  and  there  in 
the  organs  as  the  blood-current  meets  resistance  to  its  progression 
or  as  the  blood  is  drawn  into  special  organs  from  dilatation  of 
this  or  that  vascular  area.  The  quantity  of  blood  in  the  organs, 
and  the  hsemic  distribution  in  the  body  generally,  physiologically 
accommodates  itself  to  the  existing  demands.  More  blood  enters 
an  organ  when  functionating;  the  amount  traversing  it  dimin- 
ishes during  periods  of  rest.  The  nervous  stimulus  which  causes 
an  organ  to  actively  functionate,  at  the  same  induces  dila- 
tation of  its  vessels,  and  in  consequence  a  rich  supply  of  blood  is 
afforded.  This  is  especially  recognized  in  muscle.  Ranke 
determined  the  blood  content  of  the  general  musculature  of  rab- 
bits at  rest  to  be  36.6  per  cent,  of  the  total  muscle  bulk,  and  noted 
this  proportion  nearly  doubled    (66  per  cent.)    when  the  muscles 


112  Disturbances  of  Ci)'Ciilatio)i. 

were  thrown  into  tetanic  contraction.  (Internal  organs  like  the 
brain  or  intestine  may  tlms  be  relieved  of  excess  of  blood  by 
muscular  movements.)  When  the  stomach  and  intestine  are  filled 
with  food  during  digestion  they  are  much  richer  in  blood  than 
when  empty.  The  influences  which  give  rise  to  this  stimulation 
are  variable  and  multiple,  acting  sometimes  directly  upon  the 
muscular  coats  of  the  blood  vessel  wall  and  the  nervous  apparatus 
inherent  in  the  wall,  sometimes  upon  the  vascular  centre  in  the 
medulla  oblongata  (mechanical,  thermic,  electric,  chemical  irri- 
tants). 

It  is  but  a  stc])  from  the  physiological  to  the  pathological,  and 
there  is  no  sharp  line  of  differentiation ;  change  in  the  amount 
of  blood  in  a  part  becomes  a  pathological  condition  when  it  occurs 
in  an  improper  place, .  or  at  a  wrong  time,  or  if  it  exceeds  the 
normal  variations. 

Increase  in  the  quantity  of  blood  in  a  part  of  the  system,  local 
engorgement,  hypcrcoiiia,  may  be  of  one  or  other  of  two  types, 
the  result  either  of  an  excessive  influx  of  blood  to  the  part,  or  of 
a  diminished  escape  of  blood  from  the  part. 

The  first  form,  the  basic  feature  of  which  consists  of  excessive 
entrance  of  arterial  blood  into  the  tissues,  is  spoken  of  as  active 
hyperaemia,  or,  synonymously,  as  irrifafion-hyperccmia,  congestive 
hypcrccmia^  fluxion  of  blood  or  arterial  hypcrcvnua.  Increased 
supplv  of  arterial  blood  may  be  caused  by  excessive  blood  pressure. 
This  is  met  where  an  artery  is  occluded  or  some  part  of  the  body  is 
for  some  reason  prevented  from  receiving  its  proper  supply :  under 
which  circumstances  the  blood  propelled  from  the  heart  passes 
into  the  adjacent  structures  {collateral  hypcrccmia),  that  is  it 
rushes  into  the  pervious  branches  of  the  artery  near  the  obstruction, 
under  the  influence  of  the  higher  pressure.  As  a  rule,  however, 
instead  of  the  blood  being  forced  into  the  part  in  question,  there  is  a 
lowering  of  the  vascular  tension,  spoken  of  as  a  relaxation  in 
the  arterial  distribution  (relaxation-hyperccmia),  with  a  resultant 
widening  of  the  channels.  The  blood  freely  pours  into  the  dilated 
arterial  branches  and  capillaries,  and  with  increased  force ;  in  a 
w^ord  it  is  drawn  into  the  part.  The  degree  of  relaxation  depends 
largely  upon  the  lack  of  tone  of  the  smooth  muscle  of  the  vascular 
wall  and  the  congestion  is  therefore  in  such  instance  a  myoparalytic 
one.  Every  muscle  being  inseparable  from  its  innervation,  nervous 
influences  must  finally  be  regarded  as  responsible  for  changes  in 
the   vascular   tension    (tone).     It   is   assumed   that    the     vascular 


Active  Hypcrmnia.  113 

nervous  apparatus  comprises  two  types  of  nerve  fibres,  vasodilator 
and  vasoconstrictor ;  theoretically,  therefore,  stimulation  of  the 
vasodilator  nerves  should  occasion  a  widening  of  the  blood  chan- 
nels (neurotonic  congestion),  and  the  same  result  should  follow 
paralysis  of  the  vasoconstrictors  (neuroparalytic  congestion) ,  both 
of  these  influences  similarly  reducing  the  tension  of  the  muscular 
elements  of  the  arterial  wall.  This  relation  with  nervous  influ- 
ences is  well  seen  in  the  fact  that  after  section  of  the  cervical 
sympathetic  in  rabbits  the  ear  on  the  corresponding  side  becomes 
hypergemic  (CI.  Bernard),  and  after  section  of  the  splanchnics  the 
vessels  of  all  the  abdominal  viscera  become  distended  and  engorged 
with  blood  (paralysis  of  the  vasoconstrictors).  Stimulation  of  the 
nervi  erigentes  of  the  human  penis  causes  a  dilatation  of  the 
arteries  of  the  organ ;  blushing  in  man  is  brought  about  by  psychic 
influences  upon  the  dilator  centre  through  reflex  action ;  certain 
poisons,  as  nicotine  and  alcohol,  are  apparently  stimulating  to 
the  dilator  centre.  Generally  the  stinmlation  or  paralysis  of  the 
vascular  nervous  apparatus  indicated  is  the  direct  result  of  local 
influence  by  physical  or  chemical  agents.  Thus  hypergemia  may  be 
induced  mechanically  by  the  removal  of  pressure  acting  upon  the 
vessels ;  just  as  a  sponge  which  has  been  squeezed  and  is  then 
released  takes  up  water,  so  the  blood  flows  in  large  amount,  imme- 
diatelv  after  removal  of  the  pressure,  into  a  tissue  which  has  been 
deprived  of  its  blood  for  a  long  time  because  of  compression.  The 
vessels  here  do  not  at  once  regain  their  contractility,  but  are 
relaxed. 

Similarly  friction  and  scratching  can  induce  hyperemia 
mechanically,  from  the  nervous  stimulation  thus  originated. 
Thermic  influences  of  both  types  give  rise  to  hypcnemia  ;  heat  by 
its  direct  relaxing  influence  upon  the  vessel  walls,  cold  first 
causing  a  vasoconstriction  which  later  gives  place  to  a  paralyysis 
of  the  vascular  musculature.  There  is  a  special  group  of  chemical 
irritants  as  oil  of  mustard,  cantharides,  ammonia,  alcohol,  chloro- 
form, ether,  saline  solutions,  which,  either  by  stimulating  or 
paralyzing  the  nerves  of  the  vessel  walls,  cause  a  more  or  less 
intense  arterial  hyperaemia ;  these,  because  of  the  value  of  the 
hyper?emia  in  the  treatment  of  various  affections,  are  of  therapeutic 
importance  (rubefacients,  drugs  which  cause  reddening  of  the 
skin).  Probably  in  the  erythemata  which  occur  in  various  infec- 
tious diseases  there  also  exists  a  similar  toxic  stimulation  or 
paralysis  of  the  vessel  walls  either  from  the  bacteria  or  the 
microbic  products. 


114  Disturbances  of  Circulation. 

Active  hypersemia  is  essentially  an  arterial  and  capillary  dilata- 
tion. The  hyperaemic  organ  or  tissue  therefore  manifests  as  one 
of  its  features  a  red  color,  which  is  the  more  striking  the  paler  the 
tissue  normally  is,  as  in  mucous  and  serous  membranes,  and  may 
be  so  pronounced  that  the  distended  arteries  appear  as  fine  deep- 
red  lines  (branched  or  injection  erythema).  The  rapidity  of  the 
flow  of  the  blood  into  and  through  the  involved  area,  with  but 
little  output  of  its  oxygen,  causes  it  to  remain  bright  red  and 
pass  thus  into  the  veins.  In  peripheral  parts  of  relatively  lower 
temperature  previous  to  the  increased  blood  supply,  there  is  a  rise 
of  temperature  up  to  that  of  the  blood.  These  peripheral  parts, 
particularly  the  skin,  because  of  their  greater  heat  loss  and  their 
comparatively  poor  blood  supply  are  lower  in  temperature  than  the 
internal  organs  ;  but  with  the  access  of  more  blood  of  the  body 
temperature  the  skin  with  its  rate  of  heat  dissipation  unchanged 
necessarily  becomes  warmer.  The  temperature  attained  does  not, 
however,  exceed  that  of  the  internal  organs ;  and  these,  should  they 
become  hyperaemic,  do  not  suffer  any  increase  of  temperature. 
\\'here  there  is  marked  capillary  distension,  provided  the  tissues 
are  not  rigid,  there  ma}-  also  be  induced  some  swelling. 

The  results  of  arterial  hyperemia  vary  with  its  duration  and 
location.  Hyperaemia  of  the  brain  is  followed  by  unimportant  or 
marked  disturbances  of  consciousness,  dizziness  and  general  excita- 
tion (pressure  of  the  engorged  vessels  on  the  nervous  elements). 
Hyperaemia  of  the  sympathetic  nerve  does  not  cause  either  lachry- 
mation  or  salivation,  and  it  is  doubtful  whether  an  uncomplicated 
hyperaemia  causes  any  special  lymph  formation.  In  case  of  long 
continuance  of  the  hyperaemia  there  becomes  apparent  an  increased 
tissue  proliferation ;  this  is  probably  not  due  to  the  increased  blood 
supply  alone,  the  irritant  which  underlies  the  condition  having  also 
in  all  likelihood  some  stimulative  influence  in  its  causation. 

As  a  rule  uncomplicated  hyperaemia  is  a  transitory  condition ; 
with  the  disappearance  of  the  cause  for  the  vascular  relaxation  the 
contractility  of  the  arteries  returns.  Otherwise  the  hyperaemia 
may  be  regarded  as  the  precursor  and  concomitant  of  inflammation. 
Where  large  amounts  of  blood  are  drawn  into  extensive  areas  of 
hyperaemia,  a  deficiency  of  blood  (collateral  anaemia)  may  be  occa- 
sioned in  other  regions. 

Where  the  excess  of  blood  exists  in  a  part  because  of  difficulty 
in  its  exit  from  the  part  it  is  known  as  passive  hyperaemia  or 
venous  engorgement.     This  condition  is  encountered  in  connection 


Passive  Hypermnia.  115 

with  low  arterial  pressure,  the  blood  not  being  properly  propelled 
through  the  capillaries,  in  connection  with  deficiency  in  the  pro- 
pelling power  of  the   heart  and  arteries  or   complete   loss  of  the 
arterial  reactions  (atonic  hypcmmia).     When  the  blood  is  not  kept 
moving  onward,  in  compliance  with  the  law  of  gravitation  it  set- 
tles into  the  dependent  parts  of  the  body.     As  the  animal  lies  on 
one  side  the  lowest  parts  become  the  seat  of  special  engorgement 
(one  half  the  lungs  in  the  cadaver).     This  hypostatic  or  gravita- 
tion  hypercsmia    (hypostasis)    takes   place   because   of  the   longer 
persistence    of   the   blood   in   fluid   condition    in   the   capillaries   as 
compared   with   the   larger  vessels.      It   may   be   noted    in   animals 
unable   to   raise   themselves   from   the   ground    in    long  protracted 
diseases    or    in    the    agonal    period,    and    may    also    develop    after 
death.     It  may,  however,  develop  in  a  nondependent  organ  because 
of  reduction  in  its  arterial  supply,  particularly  if  the  blood  pressure 
in  the  venous  trunk  be  so  great  that  the  blood  presses  back  from 
the   veins    into   the   capillaries    no   longer   filled    from    the   arterial 
side.     Since   the   progression   of  the   blood    in   the    veins   depends 
in    part   upon    general   muscular   movements    and   the   passage    of 
blood  from  the  venae  cavse  is  particularly  favored  by  the  inspira- 
torv  expansion  of  the  thorax,  deficiency   in  body  movements  and 
in  respiratory  activity   (pulmonary  diseases),  as  may  be  expected, 
promote    the    development    of    hypostatic    congestion.      The    most 
common  obstacle  to  the  venous  circulation  arises  from  compression 
of  the  delicate  walls  of  the  veins  by  external  pressure,  kinking  as 
in  intestinal  volvulus,  constriction  or  pressure  from  tumors;  reduc- 
tion of  the  venous  lumen  or  actual   obstruction   from  thrombosis 
should  also  be  mentioned  in  the  same  connection. 

Passive  congestion  of  the  portal  vein  and  its  branches,  afifecting 
the  spleen,  stomach  and  intestines  [and  pancreas]  is  occa- 
sioned by  all  diseases  of  the  liver  accompanied  by  shrinkage  or 
reduction  of  the  capillary  network  of  the  organ,  the  condition 
interfering  with  the  progression  of  the  portal  blood  through  the 
liver. 

Widespread  passive  hyperaemia  is  met  in  case  of  cardiac  valvu- 
lar lesions  because  of  the  interferences  oflr'ered  to  the  ready  move- 
ment of  the  blood  from  the  venge  cavse  and  pulmonary  veins. 

A  passive  congestion  caused  by  local  interferences  may  have  no 
further  results  provided  the  venous  trunk  in  question  or  its  tributary 
capillaries  communicate  by  collateral  circulation  with  other  veins 
which  are  not  affected,  the  blood  then  passing  freel}-  through  such 


ii6  Disturbances  of  Circulation. 

collateral  anastomoses.  This  readily  occurs  if  such  paths  are  at  all 
numerous  and  large;  and  where  they  are  of  narrow  calibre  they 
are  gradually  widened  by  the  pressure  of  the  obstructed  blood,  so 
that  even  very  small  branches  and  capillaries  come  to  assume  con- 
siderable dimensions  permitting  the  blood  to  escape  from  the  area 
of  obstruction  practically  unhampered  (anastomotic  compensation). 
The  possibility  of  such  dilatation  depends,  however,  upon  the  degree 
and  rate  of  development  of  the  venous  obstruction  and  requires 
time.  In  the  case  of  sudden  venous  obstruction  and  the  existence 
of  few  anastomotic  channels,  before  the  collateral  branches  can 
adapt  themselves  to  the  congestion  the  disturbance  of  the  circula- 
tion may  well  induce  important  functional  and  vital  changes  in  the 
affected  organs ;  and,  of  course,  such  occurrences  are  to  be  ex- 
pected if  the  obstructed  veins  have  no  communication  with  other 
unobstructed  channels  (portal  vein,  the  veins  of  the  kidneys  and 
lungs).  Even  compression  under  the  finger  (in  phlebotomy  or  in 
a  rabbit's  ear)  will  show  how  the  impeded  blood  causes  the  veins  to 
dilate  and  swell  up ;  all  the  rest  of  the  phenomena  of  this  form  of 
hypersemia  may  be  followed  up  experimentally  in  the  exposed 
tongue  of  a  frog  or  under  the  microscope,  after  the  ligation  of 
the  larger  venous  trunks  so  that  the  blood  can  pass  out  only 
through  the  venules.  The  web  of  the  frog's  foot  may  be  employed 
for  the  same  purpose  after  ligation  of  the  femoral  vein.  At  first 
the  blood  in  the  engorged  and  expanding  veins  and  capillaries 
becomes  slowed,  then  irregular,  now  flowing  forward,  now  back- 
ward, and  sometimes  stagnates  totally.  It  can  be  seen  that  in 
some  places  the  current  is  reversed,  that  the  blood  is  passing 
out  of  the  engorged  area  through  the  collateral  branches,  these 
gradually  dilating,  and  the  stationary  or  slowly  moving  corpuscles 
gradually  being  drawn  into  the  current  and  after  a  time  the  proper 
rate  of  circulation  again  assumed. 

If  a  number  of  veins  are  occluded  or  cut  off  sufficient  to  entirely 
or  largely  prevent  collateral  compensation,  stagnation  or  stasis  of 
the  blood  takes  place.  In  the  affected  parts  of  the  vessel  the  red 
blood  corpuscles  are  packed  so  closely  together  that  their  outlines 
can  scarcely  be  distinguished  and  the  blood  completely  fills  the 
vessel  as  a  uniform  red  mass.  Stasis  becomes  especially  well 
marked  if,  while  the  venous  outlets  are  completely  closed,  the 
blood  continues  to  be  forced  in  from  the  arteries.  The  capillaries 
dilate  to  their  fullest :  their  walls,  permeable  to  the  plasma  even 
before  their  distention,  can  no  longer  hold  the  fluid  blood,  but  allow 


Passive  HypercEmia.  117 

it  to  escape  more  or  less  freely  according  to  the  pressure,  and  may 
in  fact,  rupture.  However,  even  if  the  blood  be  not  forced  into  the 
area  from  the  arteries,  exudation  of  the  fluid  part  of  the  blood 
through  the  distended  capillary  walls  may  take  place  in  ordinary 
atonic  hypostatic  congestion,  and  there  may  even  occur  a  diapcdesis 
of  red  blood  cells.  The  endothelium  and  vessel  walls  remain  intact 
only  while  they  are  being  continually  bathed  with  moving  blood  ;  and 
as  soon  as  the  circulation  stops  it  may  be  accepted  that  a  disturb- 
ance of  the  endothelial  nutrition  exists,  these  cells  then  shrinking 
and  causing  comparatively  large  open  interstices,  through  which 
exudation  takes  place.  For  these  reasons  passive  hyperemia  has 
frequently  associated  \/ith  it  a  congestion-transudation  and  haemor- 
rhage. The  latter  may  be  sufficiently  severe  to  make  the  whole 
tissue  dark  red  in  color,  infiltrated  and  completely  occupied  by 
blood   (haemorrhagic  stasis,  h?emorrhagic  infarction). 

The  pressure  occasioned  by  the  distended  vessels  and  the  fluid 
exudate,  together  with  the  impediment  to  circulation,  may  be  fol- 
lowed by  cessation  of  function  of  the  aft'ected  tissues  and  finally 
by  their  death.  The  longer  the  blood  remains  in  the  capillaries, 
slowly  giving  oft'  its  oxygen  and  capable  of  but  little  or  no  renewal, 
the  darker  it  becomes ;  the  tissues  in  venous  hyperemia  arf  there- 
fore of  a  dark  bluish  red  (cyanotic)  hue.  Such  a  tir.t  (diffuse 
cyanosis,  black  erythema)  may  be  encountered  (in  hogs)  extending 
over  practically  the  whole  surface  of  the  body  in  case  of  general 
passive  hyperaemia.  The  lack  of  oxygen  and  the  excess  of  carbon 
dioxide  in  the  venous  blood  are  partly  responsible  for  the  functional 
disturbances  arising  from  passive  hypersemia  of  the  various  organs ; 
these  conditions  act  by  stimulating  the  medulla,  and  occasion 
dyspnoea,  dizziness,  convulsions,  disturbances  of  consciousness, 
muscular  weakness  and  fatigue. 

The  superficial  external  parts  of  the  body,  when  passively  con- 
gested, become  cool  because  of  the  impeded  circulation  of  blood 
through  them,  because  the  blood  is  cooler  than  normal  and  the  heat 
dissipation  not  diminished. 

In  contrast  to  wdiat  has  been  said  above,  a  mild  but  persistent 
passive  hypersemia  is  apt  to  cause  not  only  a  swelling  of  the  organ 
affected  (kidneys,  lungs,  liver,  spleen)  because  of  the  permanent 
engorgement  and  distention  of  the  capillaries,  but  in  addition  may 
induce  an  increase  in  size  and  induration  from  the  production  of 
an  excess  of  connective  tissue  in  the  part  (Cf.  hypertrophy). 


ii8  Disturbances  of  Circulation. 

Stasis  and  stagnation  of  the  blood  may  at  times  be  caused  by  substances 
which  act  by  inducing  a  withdrawal  of  the  fluid  elements  and  thus  a 
thickening  of  the  blood  (chemicals  acting  upon  vessel  walls).  [This  can 
well  be  shown  experimentally  by  bathing  the  mesentery  of  a  frog,  arranged 
for  demonstrating  the  blood  current,  with  a  hypertonic  saline  solution,  a 
rapid  exosmosis  of  fluid  taking  place  and  the  current  being  soon  entirely 
checked,   with   the   vessels   choked  with  corpuscles.] 

Deficiency  of  blood  in  an  organ  may  be  part  of  anaemia 
of  the  general  body  (general  oligsemia  or  an?emia ;  d  priv.,  6\lyos, 
little,  and  al/xa,  blood)  or  a  consequence  of  local  impediment  to  the 
blood  current  (local  anaemia,  ischaemia,  from  taxeiv,  to  limit  or 
check).     The  blood  supply  to  any  part  mdy  be  impeded  by: 

1.  Pressure  upon  the  part  (coniprcssion  aiuvniia)  from  in- 
crease in.  the  bulk  of  adjacent  organs,  accumulations  of  fluid  or  any 
other  compressing  influence  upon  the  part  from  without,  or  by  nar- 
rowing of  the  capillaries  by  fat  deposit,  fluid  or  air  in  the  paren- 
chyma of  the  organ. 

2.  Narrowing,  occlusion  or  fault  of  contractility  of  the  arteries. 
Here  may  be  mentioned  external  pressure  upon  the  vessel,  ligation, 
occlusion  by  solid  bodies  as  by  thrombi  in  the  arterial  lumen  (cf. 
thrombosis  and  embolism) ,  rigidity  of  the  vascular  walls  from  cal- 
cification or  sclerosis  and  spasm  of  the  arterial  musculature  with 
resultant  contraction  of  the  lumen  {arterial  ancemia  or  ischccmia, 
occlusion  ancrmia,  spastic  ancemia). 

3.  In  addition,  anaemia  may  involve  a  certain  part  of  the  body 
in  case  the  general  blood  distribution  is  irregular  because  the  gen- 
eral volume  of  blood  passes  to  one  large  area  to  the  deprivation 
of  other  parts  (collateral  ancrmia);  as  when  the  posterior  parts  of 
the  body  are  markedly  infiltrated  with  blood  (symptomatic 
anthrax)  the  fore  parts  are  rendered  ansemic,  or  as  when  interna! 
haemorrhages  occur  the  flesh  is  left  ansemic,  etc. 

The  organ  or  tissue  deprived  of  its  blood  looks  pale,  the  absence 
of  the  blood  tint  permitting  the  peculiar  hue  to  become  more  appar- 
ent and  more  like  the  tissues  of  slaughtered  animals  or  like  a 
washed  tissue  deprived  of  its  blood  by  the  washing.  It  contains 
less  fluid  and  but  little  blood  appears  on  the  sectioned  surface,  and 
its  volume  is  diminished  because  of  the  emptiness  and  collapse  of 
the  vessels. 

Ansemic  parts  at  the  exterior  of  the  body,  being  exposed  to  the 
air  and  losing  their  heat,  feel  cool,  because  with  the  loss  of  blood 
their  principal  thermal  substance  is  lost  and  they  are  capable  of 
producing  little  or  no  heat  in  themselves  under  the  circumstances ; 


Local  Aiuviiiia:     IJa-uiorrha^e.  II9 

and  with  the  existing  diminution  of  nutritive  and  secretory  sub- 
stances disturbances  of  nutrition  and  diminution  of  functional 
aoility  must  ensue.  In  addition  the  products  of  previous  meta- 
bolic activity  necessarily  remain  in  the  anaemic  tissue  and  may  act 
unfavorably  upon  it.  According  to  the  grade  of  oxygen  depriva- 
tion, need  for  nutrition  and  rapidity  of  metabolism  in  the  affected 
structure  there  must  sooner  or  later  result  a  gradual  death  of  the 
anaemic  part,  because  of  the  absence  of  blood.  It  should  be  kept 
in  mind,  too,  that  the  integrity  of  the  endothelial  lining  of  the 
blood  vessels  depends  upon  the  continuous  flow  of  blood  through 
the  vessel  and  that  these  cells  gradually  degenerate  and  become 
permeable  when  the  anaemia  is  complete.  Should  the  blood  again 
flow  through  such  capillaries  which  have  been  empty  for  perhaps 
twenty-four  hours  it  readily  escapes  through  their  walls,  with  con- 
sequent haemorrhagic  infiltration  of  the  surrounding  tissues. 
(After  interruption  for  as  much  as  two  hours  the  renal  epithelial 
cells  become  necrotic  and  consequently  the  renal  function  becomes 
checked  or  ceases  entirely.)  Suspension  of  activity  in  vital  organs 
because  of  anaemia  is  a  matter  of  extreme  gravity.  Cerebral 
anaemia  is  quickly  followed  by  unconsciousness ;  and  because  of 
degeneration  of  the  central  nervous  tissue,  even  after  but  brief 
periods  of  anaemia,  this  condition  in  the  brain  and  spinal  cord  is 
likely  to  give  rise  to  destruction  of  the  ganglion  cells  and  focal 
lesions  with  symptoms  of  paralysis.  Complete  anaemia  of  the  myo- 
cardium necessarily  causes  cessation  of  the  heart's  action. 

Other  parts  of  the  system,  as  the  skin  and  muscles,  are  less  sen- 
sitive to  the  effects  of  anaemia ;  their  tissue  may  withstand  the 
condition  for  some  hours,  as  may  readily  be  appreciated  by  the 
practice  of  artificially  causing  an  anaemia  in  surgical  operations  by 
means  of  the  Esmarch's  elastic  bandages.  In  case  of  such  resistant 
parts,  if  the  cause  of  the  anaemia  be  eliminated  the  results  may  be 
but  transient  or  only  partial,  as  in  case  of  the  anaemia  of  cramps 
(spastic  anaemia)  or  anaemia  caused  by  external  pressure.  Ob- 
struction of  an  artery,  and  more  particularly  the  anaemia  resulting 
therefrom,  may  be  corrected  if  the  blood  supply  can  be  quickly  re- 
established through  the  anastomotic  vessels  (so-called  collateral 
paths). 

Loss  of  Blood;  Haemorrhage. 

The  escape  of  blood  from  the  vessels  into  the  tissue  spaces, 
bodv   cavities   or   to  the   free   surfaces   of   the   bodv   is   known   as 


I20  Disturbances  of  Circulation. 

bleeding,  haemorrhage  {al^a,  blood:  ^^705,  rupture)  or  extravasation 
{  extra,  without ;  'vas,  vessel). 

The  most  common  causes  of  haemorrhage  are  wounds  and 
lacerations  of  the  vessel  walls.  Anything  which  severs  the  con- 
tinuity of  the  vascular  wall  by  puncture,  incision,  tearing,  con- 
cussion or  contusion  affords  opportunity  for  the  effusion  of  blood 
(traumatic  liccniorrJiage).  In  the  same  way  all  conditions  which 
impair  the  resistive  strength  of  the  vessel  walls  to  the  pressure 
of  the  blood  favor  haemorrhage,  as  the  lesions  caused  by  the 
action  of  corrosive  fluids,  fatty  degeneration  of  the  walls  of  the 
vessels,  vascular  inflammations  leading  to  brittleness  and  fragility 
of  their  tissues  (corrosion  hcruiorrJiage,  spontaneous  hcemorrhage). 
Exaggeration  of  blood  pressure  (increase  of  pressure  from  sud- 
den and  powerful  cardiac  contraction  and  from  hyperVemia)  per- 
mits the  rupture  of  these  weakened  vessels,  or  perhaps  even  nor- 
mal pressure  may  be  sufficient.  Rupture  of  the  liver  is  not  infre- 
quently met  with  from  such  a  cause  after  fatty  degeneration  of  its 
vessels  and  tissues.  Or  when  the  muscle  of  an  artery  (after 
chronic  inflammation)  is  in  a  degenerate  state  its  walls  may  be 
distended  to  form  permanent  dilatations  [aneurisms]  ;  here  the  wall 
comes  to  consist  of  but  little  more  than  connective  tissue,  which 
tears  when  the  distension  becomes  great. 

Haemorrhages  of  the  types  mentioned  are  spoken  of  as  haem- 
orrhages per  rhexin  (  prj^is,  rupture;  prjyvwai,  to  burst  through),  or, 
])articularly  where  the  wall  has  been  weakened  by  pathological 
changes,  as  haemorrhages  per  diabrosin  (  bia-^i^pdocrKiLv ,  to  eat 
through ) . 

The  blood  maw  however,  leak  out  of  the  smaller  vessels, 
capillaries  and  veins,  without  the  apparent  existence  of  any  lesion 
in  the  continuity  of  structure,  because  of  some  abnormal  pemie- 
ability  of  their  walls.  Such  haemorrhage  is  known  under  the 
names  diapedesi::,  or  luemorrhage  per  diapedesin  ( from  Sia-v-ndav, 
to  burst  through).  The  increased  permeability  of  the  vessel  wall 
is  explained  by  the  fact  that  under  the  influence  of  toxic,  infec- 
tious, thermic  or  other  injurious  agencies,  as  well  as  from  marked 
engorgement  and  distension  of  the  capillaries  (passive  hyperaemia, 
stasis),  the  cement  substance  between  the  endothelial  cells  becomes 
porous ;  for  example,  the  endothelial  cells  may  shrink  into  globular 
form  and  separate  from  each  other,  or  openings  may  result 
from  destruction  of  the  cells.  The  red  corpuscles  then  slip 
through  between  the  cells  or  are  forced  out  along  with  the  plas- 


Hemorrhage. 


121 


inatic  exudate ;  because  of  their  elasticity  these  corpuscles  are 
easily  able  to  pass  through  the  most  minute  clefts  of  the  cement 
substance.  There  exist  therefore  in  these  cases  minute  micro- 
scopic tears.  Haemorrhage  by  diapedesis,  however,  may  assume 
important  proportion  and  may  be  fatal  because  of  its  location  (as 
in  the  brain  or  stomach)   or  of  its  duration. 

Since  it  is  the  bathing  of  the  endothelium  with  nonnal 
blood  which  is  essential  to  its  integrity,  it  may  be  easily  appre- 
hended that  even   a  temporar\-   interruption   of  the   circulation   to 


FU 


1. 


Mesentery  of  the  dog.  (a)  IliPmoirhago  by  diapedesis.  (b)  Ecchymosis 
occurring  in  a  similar  manner,  tlie  opening  in  the  wall  of  the  cajiillary 
having  closed  up  again.  The  figure  aU-o  t-.hows  an  emigration  of  leucocytes. 
Magnified  2.50  times.      I  After  Thoma. ) 


the  capillaries  may  render  them  abnormally  permeable  and  be  the 
cause  of  diapedesis  after  restoration  of  the  flow  (cf.  oiibolisDi). 

Haemorrhages  are  also  classed  according  to  the  type  of  vessel 
from  which  the  blood  escapes,  as  arterial,  z'enous  and  capillary 
hcemorrhagcs ;  where  the  blood  oozes  from  a  widely  diffused  fault 
in  the  softer  tissues,  as  in  the  liver,  and  the  type  of  the  bleeding 
vessel  cannot  be  made  out,  the  term  parenchymatous  hcemorrhage 
is  appropriate. 

The  blood  may  escape  freely  to  the  exterior  of  the  body  or 


122  Disturbances  of  Circulation. 

into  one  of  the  internal  body  cavities  (external  and  internal  hcemor- 
rliage,  surface  hcumorrhage  and  hccmorrhage  into  a  cavity).  When 
the  exuded  blood  fills  the  tissue  spaces  and  completely  saturates 
the  tissvies,  the  terms  ]ia:niorrhagic  infiltration  or  hccniorrhagic  in- 
^  farction  {infarcere,  to  stop  up  or  fill  up)  are  applied,  the  latter  term 
being  used  particularly  when  the  blood  coagulates  in  the  tissue 
and  remains  in  it  as  a  dense  compact  mass  [usually  in  a  definite 
circumscribed  area  of  infiltration  further  described  in  connection 
with  embolism].  If  the  bloody  effusion  causes  an  extensive, 
loose,  gelatinous  swelling  of  the  tissue,  diffusely  filling  the 
structure  [applied  particularly  to  infiltration  beneath  some  sur- 
face], it  is  spoken  of  as  a  suffusioii  {suffundcre,  to  pour)  or 
snggillation.  Small  circumscribed  foci  of  haemorrhage,  apparent 
as  spots  and  points  from  which  the  blood  cannot  be  discharged 
by  pressure  (especially  in  serous  membranes),  are  called  hccmor- 
rhagicc  niacnlosce,  eccJiyinoscs  [xv/Modv.to  overflow),  petechice  (from 
pidoccliio,  louse  or  its  bite;  or  from  pediculce  flea-bites  [petigo, 
eruption]),  or  vihiccs  when  in  streaks  {zibc.v^  a  streak).  When 
the  extravasated  blood  collects  in  a  rounded  mass,  as  when  it 
dissects  u[)  the  capsule  of  an  organ  or  a  connective  tissue 
structure,  or  when  it  accumulates  in  a  cavity  or  becomes 
encapsulated  by  a  surrounding  inflannnatory  zone,  the  mass 
is  spoken  of  as  a  hccniatonia  (blood  boil)  or  hccniorrhagic  cyst. 
Special  terms  are  also  employed  for  these  effusions  of  blood 
depending  upon  their  location :  an  extravasation  of  blood  into  the 
pleural  cavity  is  termed  hccmothorax ;  into  the  peritoneal  sac, 
hcemoccclia  (  koiXIo.,  the  body  cavity)  ;  into  the  pericardial  cavity, 
ha:mopericardium ;  into  the  uterus,  hcematometra  (fj.r}Tpa,  uterus)  ; 
into  the  sac  of  the  tunica  vaginalis  testis,  hccniatocele  (/ctjXt?,  rupture). 
In  addition  special  names  have  always  been  made  use  of  in  con- 
nection with  haemorrhage  from  special  organs :  epistaxis  ( iin-aTA^iiv, 
to  drip)  for  nasal  haemorrhage;  liccniaturia  (o^pov,  urine)  for  the 
escape  of  blood  with  the  urine ;  hcrniafcniesis  ( efieiv,  to  vomit) 
for  gastric  haemorrhage  (also  melcrna,  fieXaiva  vocros,  from  /xAas,  black, 
because  of  the  dark  brown  color  given  the  blood  by  the  gastric 
juice)  ;  haemoptysis  {ittvuv,  to  spit)  for  expectoration  of  blood  from 
the  lungs ;  metrorrhagia  for  haemorrhage  from  the  uterus ; 
hccnwrrliagic  apoplexy  {dirowXiffanv,  to  strike  down,  to  stun)  for 
Spontaneous  haemorrhage  of  the  brain. 

Symptoms  and  Results.  From  its  characteristic  blood  tint  an 
eft'usion  of  blood  is  easily  recognizable  anatomically  as  a  dark  red 
accumulation  of  blood,  or  spot  which  cannot  be  effaced  and  which 


Hemorrhage. 


123 


is  more  or  less  sharply  circumscribed.     Upon  surfaces   or   in  the 
body    cavities    the    extravasation    presents    a    striking    picture,    in 
profuse,  partly  coagulated,  partly  fluid  masses,  or  in  a  gelatinous, 
red,    jelly-like    tumor    ex- 
tending into  the  loose  sub- 
cutaneous   or    sub-mucous 
tissue      (haeniorrhage     fol- 
lowing   contusions    of    the 
abdominal     walls,    hremor- 
rhagic    stasis    of    the    in- 
testinal    m  u  c  o  u  s     mem- 
brane), or  sharply  outlined 
in  numerous  definite  drop-      h 
like  flecks   (not  effaced  on     % 
pressure)    as    seen    in    the      ^ 
sub-serous    cellular    tissue 
of  the  pleura,  pericardium 
and    epicardium.       In    the 
secretions    it   is   easily    ap- 
preciated   by    the   more   or 
less  pronovmced  blood  tint 
which  it  imparts  to  them  ; 
the  intestinal  contents  may 
assume  a  slightly  reddish - 
gray,  cafe-au-lait  color  up 
to  a   chocolate    brown    or 
pure    blood-red    from    the 
admixture    of    blood ;    the 
gastric    contents    a    sepia- 
brown,  the  urine  a  blood- 
red  to  black;    the  expecto- 
rate and  nasal  secretion  a 
rusty,     red-streaked     or 
foam  y     red     appearance 
(pulmonary  oedema). 

While  it  is  usually  easy 
to  detect  the  ruptured  ves- 
sel    in     case     of     massive 

haemorrhages  (as  a  ruptured  aneurism,  the  eroded  stump  of  a  ves- 
sel in  hemorrhage  from  gastric  ulcers),  and  the  infiltration  of 
blood  surrounding  the  lesion  in  the  organ  points  to  the  origin 
of     the     haemorrhage     and     indicates     its     intravital     occurrence, 


Fig.   2. 

Ilaematoma    of    the    spleen    of    horse. 


124  Disturbances  of  Circulation. 

yet  in  capillary  diapedesis  from  a  mucous  membrane,  as  the  gastric 
or  intestinal  lining,  the  points  of  escape  are  invisible  to  the  naked 
eye,  and  only  the  blood  deposit  on  the  surface  and  the  pallor  of  the 
mucous  membrane  indicate  the  fact  of  extravasation.  Arterial 
haemorrhages  are  recognized  in  living  animals  by  the  bright  red 
color  of  the  arterial  blood,  by  the  spurting  character  of  the  escaping 
stream  from  the  larger  arteries,  the  spurts  corresponding  to  the 
cardiac  contractions ;  while  the  bleeding  from  the  veins  is  con- 
tinuous and  without  pulsation.  However,  an  arterial  spurting  may 
be  prevented  by  the  interposed  parenchyma  (Samuel).  If  the  larger 
vessels  between  the  point  of  haemorrhage  and  the  heart  be  com- 
pressed the  haemorrhage  will  diminish  if  it  be  arterial ;  it  will  be 
increased  if  venous. 

The  results  of  hcoiwrrJiage  depend  upon  the  quantity  and  the 
duration  of  the  bleeding,  as  well  as  the  location  of  the  lesion.  In 
case  of  loss  of  over  one-third  of  the  total  volume  of  blood  (about 
3  to  4  per  cent,  of  the  body  w^eight ;  the  average  total  quantity 
being  from  one-tenth  to  one-twentieth  of  the  weight  of  the  body), 
the  flow  continuing,  the  blood  pressure  falls.  The  vessel  walls, 
although  capable  of  wide  adaptation  to  the  volume  of  blood  within, 
have  become  too  wide  for  the  diminished  amount  and  cannot  longer 
advantageously  propel  it.  A  general  oligaemia  has  been  established, 
indicated  by  the  pallor  of  the  mucous  membranes,  dizziness,  faint- 
ing (^an^mia  of  the  brain)  and  convulsions,  and  the  animal  may 
bleed  to  death.  These  results  occur  not  only  when  the  haemorrhage 
is  external,  but  also  in  copious  haemorrhages  into  the  intestinal 
lumen,  peritoneal  cavity,  etc.    (internal  haemorrhage). 

Haemorrhage  gradually  ceases  by  the  closure  of  the  opening  in 
the  vessel  from  the  formation  of  a  blood  coagulum  in  the  opening 
(adhesion  thrombus),  the  closure  being  facilitated  by  constriction 
of  the  vascular  lumen  (contraction  of  the  wall),  external  pressure 
(by  the  tissue  engorged  with  blood),  and  by  the  fall  of  blood 
pressure.  After  such  cessation  the  volume  of  the  fluid  portion  of 
the  blood  is  soon  restored.  The  watery  element  first  passes  into 
the  vessels  from  the  tissues  and  for  a  time  the  blood  is  conse- 
quently more  fluid  (hydraemic)  than  before  the  haemorrhage;  but 
gradually  the  blood  cells,  regain  their  normal  numbers  as  their 
regeneration  (cf.  chapter  on  regeneration)  proceeds  in  the  blood 
forming  organs. 

At  the  site  of  haemorrhagic  infiltrations  the  tissues  present  more 
or   less    functional   alteration.     The   presence   of   the   extravasated 


Hcem  0  rrhage.  125 

mass  of  blood  exerts  a  certain  amount  of  pressure  and  in  conse- 
quence the  cells  and  tissues  are  forced  apart,  displaced  by  the  in- 
vading blood ;  and  hollow  viscera  are  occluded  by  the  coagulated 
blood.  Even  small  haemorrhages  in  the  brain,  according  to  their 
precise  location,  occasion  a  loss  of  function  in  the  area  affected, 
perhaps  even  to  the  extent  of  complete  obliteration  of  conscious- 
ness ;  in  the  case  of  spinal  haemorrhages  palsies  ensue :  hccmorrhage 
under  the  mucous  lining  of  the  air  passages  (fracture  of  the 
trachea  and  larynx)  forces  the  same  into  the  lumen  to  such  a 
degree  that  the  air  passage  is  constricted  and  death  from  asphyxia 
may  result. 

The  escaped  blood  usuall}^  coagulates,  precisely  as  the  blood  in 
venesection  (cf.  chapter  on  thrombosis).  Should  this  clot  remain 
in  the  tissue  or  in  one  of  the  serous  sacs  it  acts  as  an  inflammatory 
excitant ;  it  attracts  the  leucocytes  by  chemotaxis  and  causes  a 
limiting  zone  of  connective  tissue  proliferation  about  it.  This 
gradually  forms  a  capsule  about  the  collection  of  blood,  transform- 
ing it  into  a  haemorrhagic  cyst,  often  called  a  haematoma,  in  which 
the  disintegrating  blood  exists,  partly  as  soft,  elastic,  fibrinous 
masses,  of  a  reddish  or  brownish  color,  partly  as  liquid  serum  ex- 
pressed from  the  clot.  Such  h.Tmatomata,  sometimes  approaching 
the  size  of  a  human  head,  are  not  infrequently  seen  in  the  spleen 
of  domestic  animals,  around  the  kidneys  in  swine,  and  in  the  pelvic 
cavity  of  cattle  as  the  results  of  contusion  haemorrhages.  On  the 
other  hand  the  penetration  of  leucocytes  to  the  mass  and  the  pro- 
liferation of  fibroplastic  and  angioplastic  tissue  leads  to  the  resorp- 
tion of  the  blood.  Its  disintegrating  elements  are  taken  up  by 
the  amoeboid  cells  and  carried  away ;  the  plasma  is  absorbed  by 
the  cells  and  may  pass  off  through  the  lymph  paths.  The  red 
corpuscles  both  in  the  tissue  lymph  and  in  the  blood  vessels  begin 
to  swell  and  lose  their  color  or  to  become  shriveled.  The  coloring 
matter,  haemoglobin,  having  been  dissolved  out  may  soak  through 
the  tissue  dift"usely  or  may  become  deposited  in  the  form  of  flakes, 
granules  or  more  rarely  as  crystals  through  the  tissue.  The 
crystalline  form  is  especially  apt  to  occur  where  the  blood  has  been 
stagnant  (haematoma),  appearing  as  ruby-red  to  brown,  minute 
rhombic  plates  and  needles  (iron-free  haematoidin)  ;  the  granules 
are  yellow  and  angular,  sometimes  give  an  iron  reaction  (haemosi- 
derin),  sometimes  undergo  a  change  like  the  crystals  b\'  which  the 
iron  is  separated  from  the  haemoglobin,  iron-free  haematoidin 
(haemofuscin)  remaining. 


126  Disturbances  of  Circulation. 

This  blood  precipitate  is  found  microscopically  not  only  at  the 
site  of  haemorrhage,  especially  in  the  amoeboid  cells  which  are 
loaded  with  it,  but  also  in  the  nearest  lymph  glands  which  are  often 
found  tinted  all  through  by  a  rusty,  reddish-brown  color  from  the 
quantity  of  blood  pigment  conveyed  to  them.  In  the  dead  body,  on 
account  of  sulphur  products  (sulphuretted  hydrogen)  of  the 
cadaveric  bacteria,  the  site  of  a  haemorrhagic  infiltration  may  be 
found  changed  to  a  slate  gray  to  black  hue  by  the  sulphur  com- 
binations ;  in  life,  too,  in  places  where  similar  bacterial  accumula- 
tions and  fermentations  occur  (intestine,  abscess  cavities,  fistulous 
paths,  mycotic  diseases  of  the  bladder)  the  pigment  may  undergo 
the  same  changes  in  color  and  thereafter  remain  as  evidence  of 
previous  haemorrhage. 

Dropsy.  Hydrops  and  Oedema. 

Excessive  accumulation  of  the  tissue  fluid  or  lymph  in  the 
lymph  spaces,  lymph  vessels  and  serous  sacs  (Ivmph  sacs)  is 
spoken  of  as  dropsy,  hydrops  (from  vSa>p,  water)  or  hydropsia, 
and.  if  the  accumulation  has  occasioned  swelling  of  the  tissue,  as 
oedema  (from  or5a;'.  to  swell).  The  process  itself  is  described  as 
a  dropsical  transudation  (from  sudarc,  to  sweat)  ;  the  accumulated 
fluid  as  a  transudate.  Neither  the  process  nor  the  transuded  fluid 
is  essentially  anything  more  than  a  quantitative  disturbance  of 
physiological  lymph-production.  Lymph  is  originally  derived  from 
the  blood,  and  is  regarded  by  many  as  a  secretory  product  of  the 
endothelium  of  the  capillaries,  although  the  blood  pressure  is  also 
maintained  as  a  factor  in  its  production  and  accumulation,  affecting 
the  filtration  of  the  liquid  part  of  the  blood  through  the  capillary 
walls.  [Whether  the  physical  processes  of  dialysis  and  osmosis 
should  also  be  invoked  here  is  debated.  Lazarus-Barlow,  in  dis- 
cussing the  vital  transudation  of  lymph,  urges  the  importance  of 
tissue  demands  for  lymph  both  for  purposes  of  nutrition  and  for 
its  influence  in  diluting  and  removing  various  products  of  their 
metabolic  activities  or  of  their  degeneration,  and  points  out  that 
in  this  last  case  there  exists  a  possible  explanation  for  the  per- 
sistence of  an  oedematous  process  in  case  the  excretory  organs  as 
the  kidneys  fail  of  eliminating  from  the  blood  the  various  waste 
materials.  Thus  if,  in  a  case  of  nephritis,  the  blood  becomes  sur- 
charged with  waste  materials  and  if  at  the  same  time  such  waste 
in  a  local  area  of  special  activity  or  of  degeneration  is  excessive, 


Dropsy.  127 

the  tissue  demands  for  increased  transudation  are  increased  in 
order  to  acconiplisli  its  removal  by  the  lymph ;  yet  if  the  blood 
already  contain  an  excess  of  the  very  substance  in  question  the 
increased  transudation  only  serves  to  more  nearly  complete  a 
vicious  cycle,  and  adds  to  the  existing  accumulation.]  Two 
reasons  may  be  assumed  for  the  pathological  increase  of  this 
fluid  in  the  tissues,  either  an  obstruction  to  the  lymph  drainage, 
or  an  unusual,  exaggerated  transudation  ;  both  of  which  factors 
may  be  operative  at  the  same  time.  In_  view  of  the  free  anasto- 
mosis and  the  great  abundance  of  lymph  channels,  together  with 
the  fact  that  lymph  absorption  is  also  accomplished  by  the  capil- 
laries and  veins,  obstruction  of  isolated  lymph  channels,  it  may 
be  said,  does  not  ordinarily  occasion  lymph  stasis.  Even  in  case 
of  unusual  formation  of  lymph  there  is  no  essential  reason  for 
determination  of  any  abnormal  condition,  as  within  certain  limits 
the  paths  of  lymphatic  drainage  are  capable  of  accommodating 
and  carrying  ofl:"  large  quantities  of  fluid,  provided  the  tissues 
retain  their  ]iroper  elasticity  (Landerer),  and  the  propulsive 
forces  (muscular  movements,  etc.)  are  of  normal  functional  ex- 
cellence. It  is  only  when  the  increased  transudation  becomes  ex- 
treme and  the  lymphatic  flow  fails  to  keep  pace,  that  cedema 
develops. 

The  most  common  cause  for  such  fault  is  passive  hyperemia. 
In  case  of  passive  congestion  the  blood  pressure  in  the  capillaries 
becomes  raised  and  the  current  of  blood  slowed,  as  a  result  of 
which  the  endothelium  of  the  walls  of  the  capillaries  becomes  ab- 
normally permeable  and  in  conseqtience  the  fluid  element  of  the 
blood  exudes  profusely.  This  exudate  is  usually  not  as  rich  in 
albumen  as  the  normal  lymph.  As  examples  of  oedema  of  this 
type  may  be  suggested  that  caused  by  compression  (as  oedema 
of  the  lips  by  application  of  twitches  to  a  horse's  mouth),  by 
venous  thrombosis,  by  cardiac  lesions  which  impair  the  current 
of  blood  in  the  ven^e  cavie,  by  pulmonary  changes  which  prevent 
proper  progression  of  blood  from  the  right  heart,  by  structural 
faults  of  the  liver  causing  obstruction  of  the  portal  capillaries  and 
producing  portal  congestion  (dropsy  or  cedema  from  passive 
congestion).  Coincident  interference  with  lymphatic  drainage 
may  be  determined  perhaps  by  the  pressure  of  fluid  accumulations 
in  the  thoracic  or  peritoneal  cavities  upon  the  thoracic  duct,  per- 
haps by  the  loss  of  natural  elasticity  of  the  tissues,  stretched  and 


128  Disturbances  of  Circulation. 

distended  by  the  increased  and  persistent  pressure  of  the  lymph- 
atic transudate. 

Increased  transudation  is  observed  also  in  connection  with  in- 
flammation and  changes  of  the  vascular  walls  caused  by  toxic 
chemical  agents  acting  either  locally  or,  when  circulating  in  the 
blood,  widely  {irritative  or  inflammatory  dropsy).  One  should 
recall  in  this  relation  the  influence  of  the  slowing  of  the  blood 
current  and  vascular  dilatation,  together  with  possible  shrinkage 
and  separation  of  the  endothelial  cells,  combining  to  render  the 
vessel  walls  more  permeable ;  moreover,  a  number  of  poisons,  as 
some  of  the  products  of  metabolism,  seem  to  directly  stimulate 
the  endothelium  to  increased  secretory  activity,  to  possess  what 
might  be  called  a  "lymph-driving"  ( lymphogogue)  action.  In 
addition  it  may  be  pointed  out  that  in  inflamed  tissues  the  lymph 
flow  is  impaired  by  the  fact  that  the  inflammation  occasions 
coagulation  of  the  lymph  and  impairs  the  elasticity  of  the  tis- 
sues. Such  features  explain  the  occurrence  of  cedema  around 
tissues  which  are  the  seat  of  purulent  or  hsemorrhagic  inflamma- 
tion   (collateral  cedema). 

Dropsy  is  often  concurrent  with  wasting  diseases  and  abnormal 
states  of  the  blood  characterized  by  poverty  of  its  cellular  ele- 
ments and  increase  in  its  jiroportion  of  water,  the  so-called 
cachectic  or  hydremic  wdenia,  as  seen  in  cases  of  pulmonary 
verminosis,  fluke  disease  of  the  liver  and  chronic  parenchymatous 
nephritis.  It  is  an  open  question  in  such  cases  whether  the  es- 
sential fault  in  determining  the  dropsy  is  the  dilution  of  the 
blood  which  may  perhaps  make  it  filter  more  readily  through  the 
vessel  walls,  or  whether  we  should  ascribe  it  to  the  presence  of 
metabolic  products  and  other  toxic  matter  in  the  circulating 
blood  impairing  the  vascular  endothelium  and  permitting  the 
transudation  because  of  an  increased  permeability.  (Cohnheim 
and  Lichtheim  failed  to  obtain  dropsy  by  introducing  large  quan- 
tities of  sodium  chloride  solution  into  the  blood  of  experiment 
animals,  even  when  as  much  as  half  of  the  blood  was  replaced 
by  the  saline  solution ;  Gartner,  however,  succeeded  in  causing 
an  oedema  in   dogs  by  long  continued  infusion  of  salt  solution.) 

No  satisfactory  explanation  exists  for  the  rather  common 
congenital  anasarca  of  aborted  calves.  According  to  the  investi- 
gations of  L.  Franks  the  thoracic  duct  is  sometimes  missing  in 
these  "watei:  calves"    (or   "Dunstkalbern")  :   while   in   other  cases 


Dropsy. 


129 


renal  changes,  perhaps  the  sequels  of  an  intrauterine  nephritis,  are 
met  which  may  occasion  dropsies  because  of  retention  of  water 
or  on    account  of   some  infectious  toxic   influence  present. 

The  dropsical  transudate  is  usually  a  colorless  or  wine-yellow 
water-like  fluid,  generally  containing  a  smaller  proportion  of 
albumen  than  the  lymph  and  fluid  exudates,  as  a  rule  showing 
only  0.1    to   0.8   per   cent,    albumen,    according   to    Perls    up   to    5 


Fig  3. 

Anasarca    universalis    congen.,    so-called    water 


calf. 


per  cent.  (Lymph  and  blood  plasma  contain  about  7  per  cent.) 
The  proportion  of  salines  is  the  same  as  in  the  plasma  (0.8  per 
cent).  [The  precise  composition,  particularly  as  relates  to  pro- 
teid,  varies  in  the  different  types  of  dropsical  fluid;  and  even  hi 
the  same  subject  the  amount  of  proteid  is  not  identical  in  fluid 
from  different  parts  of  the  body,  that  from  the  subcutaneous 
tissue  being  usually  marked  by  the  lowest  proteid  content,   while 


130  Disturbances  of  CirciilatioJi. 

that  from  the  serous  cavities,  especially  the  pleura,  is  apt  to  be 
richer  in  albumen.]  In  case  of  coincident  escape  of  blood 
corpuscles  (in  passive  hypersemia)  admixture  of  these  elements 
with  the  transudate  may  occur  to  a  sufficient  extent  to  give  it  a 
blood-red  color  and  occasion  fibrin  deposition  {^hydrops  hcemor- 
rhagicus).  In  other  instances  admixture  of  fat  from  the  blood 
or  from,  fatty  degeneration  of  the  cellular  elements  macerated  in 
the  fluid  may  give  a  milky  appearance  to  it  (hydrops  adiposus, 
chyliformis)  ;  and  in  abdominal  dropsy  a  similar  appearance  may 
be  occasioned  by  rupture  of  the  chylous  vessels  and  admixture  of 
chyle  with  the  fluid   (hydrops  chylosus). 

The  amount  of  fluid  in  the  large  body  cavities  may  reach  con- 
siderable volume,  10.  50  to  100  liters  in  large  domestic  animals. 
Such  quantities  of  fluid  are  naturally  capable  of  exerting  marked 
pressure  upon  the  dift'erent  adjacent  organs,  and  distend  the  walls 
of  these  cavities.  Consequently  in  case  of  ascites  the  peritoneal 
cavity  is  considerably  enlarged  and  becomes  a  fluctuating  sac ;  the 
pericardial  sac  attains  a  wide  outline  and  fluctuates ;  and  even  the 
chest  wall  may  be  distended  and  barrel-shaped  from  the  separation 
and  outward  displacement  of  the  lower  ribs.  In  the  foetus,  in 
which  the  fontanelles  are  still  yielding,  the  covering  of  the  brain 
becomes  a  huge  sac.  partly  membranous,  partly  made  up  of  the 
cranial  bones  forced  apart  and  transformed  into  thin  plates. 
When  the  transudate  fills  the  spaces  of  a  tissue  the  porous  cellular 
structure  becomes  a  gelatinous,  amber-colored,  swollen  mass, 
from  the  cut-surface  of  which  a  serous  fluid  drips  and  whose 
doughy  swelling  retains  for  a  long  time  the  pressure  marks  of  a 
finger.  Sometimes  bladder-like  collections  or  cysts  may  form 
from  the  forcible  distension  of  the  connective  tissue  spaces. 

Various  terms  have  by  custom  been  applied  to  these  accumula- 
tions of  transuded  fluid.  CEdema  of  the  skin  is  spoken  of  as 
anasarca  (from  avi  and  adpi,,  flesh;  supply  hydrops):  collec- 
tions in  the  pleural  cavities  as  hydrothorax ;  in  the  pericardial  sac, 
hydropericardhim;  in  the  peritoneal  cavity,  ascites  (from  d<r/c6s, 
bell}' ;  namely,  hydrops  ascites)  ;  in  the  tunica  vaginalis  testis, 
hydrocele  (from  v5wp-Kr)\-n .  water  rupture)  ;  in  the  cranial  cavity, 
hydrocephalus. 

The  result  of  the  oedema  depends  upon  the  location  and  cause 
of  the  condition.  Local  dropsies  of  the  skin  may  last  a  long 
time,  but  eventually  disappear  after  the  removal  of  the  cause 
and  the  resorption  of  the  fluid.     CEdema  of  the  tissues  about  the 


Thrombosis.  137 

laryngeal  entrance  (oedema  of  the  glottis)  is  dangerous,  occasion- 
ing asphyxiation  by  narrowing  the  air  passages;  oedema  of  the 
lungs  and  of  the  brain  may  be  fatal  by  causing  functional  dis- 
turbances of  these  organs.  The  mechanical  pressure  effects  of 
collections  of  fluid  in  tlie  serous  cavities  upon  the  blood  circula- 
tion, the  compression  and  displacement  of  viscera  (pressure  on 
the  diaphragm),  as  secondary  results  of  the  dropsy,  increase  the 
severity  of  the  primary  disease  which  was  the  cause  of  the  dropsy 
(affections   of   the   heart,   liver    or   kidneys). 

Obstruction  of  Blood  Vessels.     Thrombosis  and  Embolism. 

Obstruction  of  blood  vessels  may  be  due  to  the  formation  within 
them  of  relatively  solid  plugs  made  up  of  the  blood  constituents, 
this  process  being  known  as  thrombosis  ( 6  ep6ix(3os,  mass;  from 
rp^cpw,  to  make  firm  or  compact),  or  to  forcible  lodgment  in  their 
limien  of  materials  conveyed  by  the  blood  current,  this  latter  pre  cess 
being  known  as  embolism  ( e/j.-pdWeiv .  to  throw  in). 

It  is  well  known  that  blood  outside  the  body  clots  in  a  few 
minutes  after  its  escape  from  the  vessels,  as  after  venesection. 
There  is  formed  from  the  blood  a  red  jelly-like  mass,  the  bloody 
cnior  saiigiiinis:  over  the  surface  of  which  there  collects  a  pale 
yellow  fluid,  the  blood  serum.  The  clot  is  primarily  constituted 
of  fibres  of  coagulated  fibrin,  which  include  the  blood  plaques.  In 
case  of  slow  coagulation  the  red  corpuscles  sink  to  the  bottom  of 
the  containing  vessel  and  thus  the  superior  part  of  the  coagulum  is 
largely  occupied  by  the  lighter  and  therefore  less  readily  sinking 
white  blood  corpuscles ;  for  which  reason  the  surface  of  the  clot 
shows  a  yellowish-white  layer  composed  of  fibrin  and  leucocytes, 
the  so-called  huffy  coat.  The  formation  of  fibrin  is  the  main  fea- 
ture of  extravascular  coagulation,  and  can  be  directly  followed  in  a 
drop  of  blood  under  the  microscope.  In  a  blood  drop  placed  upon 
the  cold  slide  the  film  can  be  observed  to  separate  as  fine  threads, 
and  these,  with  the  platelets  adhering,  unite  with  each  other  to  form 
a  network  (Birch-Hirschfeld).  Fibrin  is  an  albiuninous  substance, 
existing  in  solution  in  the  circulating  blood  in  the  plasma  (the 
so-called  fibrinogenous  material  or  fibrinogen),  which  separates  as 
a  coagulating  calcium  compound  with  proteid  when  acted  upon  in 
th.e  presence  of  calcium  salts  by  a  ferment  known  as  the  fibrin 
ferment. 

Following   the   apt    comparison    of    Birch-Hirschfeld,    blood    coagulation 
rnay  be  thought  of  as  somewhat  analogous  to   rennet   coagulation   of  milk. 


132  Disturbances  of  Circulation. 

In  the  presence  of  lime  salts  of  the  milk,  casein  (which  is  similarly  a 
calcium  proteid  combination)  is  separated  from  the  milk  bj'  the  lab- 
ferment,   leaving   a   serum,    the    \vhe\-. 

Coagulation  of  blood  may  be  checked  or  inhibited  by  certain 
chemicals  which  destroy  the  fermeiit  or  which  dissolve  the  fibrin 
immediately  after  it  is  formed  (potassium  citrate,  or  oxalate,  extract 
of  the  cephalic  glands  of  the  leech).  [Extract  of  the  cephalic  end 
of  the  hookworms  of  the  dog  possesses  a  similar  property.] 
So,  too,  coagulation  fails  if  the  inner  surfaces  of  the  vessel  in  which 
the  blood  is  caught  be  covered  with  vaseline,  thus  preventing  adhe- 
sion  (Freund). 

After  death  the  blood  clots  qtiickly  and  in  a  manner  similar  to 
extravascular  coagtilation,  especially  in  the  heart  and  larger  vessels ; 
in  the  capillaries  it  remains  fluid  for  a  longer  time.  In  the  presence 
of  toxic  substances  having  solvent  action  upon  the  blocxl  and  fibrin, 
too,  coagulation  is  incomplete  (hccmolytic  sttbstances,  as  some  of 
the  bacterial  products,  presence  of  excessive  amounts  of  carbon 
dioxide  in  the  blood).  Cadarcric  clots  are  homogeneotis.  soft, 
elastic,  gelatinous  masses  which  look  like  casts  of  the  vessels,  are 
without  lamination,  and  are  either  of  a  dark  red  color  throughout 
or  of  a  more  or  less  yellowish  gray  to  amber  hue  with  jelly-like 
semi-transparent  appearance.  The  latter  form,  comparable  to  the 
"buffy  coat"  are  met  in  anaemic  states  and  gradual  cardiac  failure, 
the  blood  cells  in  such  instances  settling  and  the  fibrin  containing  a 
large  amount  of  serum.  [In  these  heart-clots  the  dark  red  homo- 
geneous examples  are  commonly  interpreted  as  indicating  rapid 
death  and  quick  coagulation  before  the  corpuscles  have  had  time 
to  separate ;  they  are  thus  referred  to  as  post-mortcui  clots.  On 
the  other  hand,  the  yellowish  translucent  coagula.  occurring  in  slow 
circulatory  failtire,  are  often  spoken  of  as  aiifc-iiiortciii  clots,  from 
the  idea  that  they  form  or  start  to  form  during  the  period  of  slow- 
ing of  the  current  prior  to  death,  the  red  cells  at  least  sinking 
more  or  less  from  the  general  blood  volume  prior  to  the  actual 
stoppage  of  the  current  and  coagulation  of  the  blood.] 

Coagulation  and  thrombus  formation  within  the  vessels  of  the 
living  takes  place  from  the  following  causes  or  favoring  conditions : 

I.  Entrance  of  chemicals  into  the  circulation  favoring  coagula- 
tion of  the  blood  (fcnunit  thrombosis) :  B\-  the  injection  of  ether 
and  other  chemicals,  the  introduction  of  substances  destructive  to 
the  leucocytes,  injections  of  emulsions  of  various  parenchymatotis 
tissues   (brain,  adrenals)   or  of  the  expressed  juices  of  the  thymus 


Thrombosis. 


133 


body,  testicles,  etc.,  or  of  laked  or  altered  blood,  it  is  possible  to 
bring  about  extensive  coagulation  witb  fatal  effect.  Such  experi- 
mental findings  warrant  the  assumption  that  the  occurrence  of 
tiirombosis  is,  at  times,  in  infections  and  diseases  accompanied  by 
tissue  destruction  dependent  upon  the  coagulative  action  of  microbic 
poisons  or  tissue  products  permitting  the  formation  of  fibrin  fer- 
ment by  the  disintegration  of  leucocytes. 

2.     Slowing  and  cessation  of  the  blood  current :    It  has  been 


Fig.  4. 
Cardiac   valvular   thrombosis    (right   ventrical  of  heart  of  hog). 


shown  by  experiment  that  after  double  ligation  of  a  vein  or  artery, 
although  the  blood  in  the  segment  between  the  ligatures  is  entirely 
stagnant,  it  may  remain  fluid  for  months  (Baumgarten,  Senftleben 
and  others).  Nevertheless  in  situations  where  blood  vessels  are 
expanded,  particularly  when  the  seat  of  pathological  dilatations,  and 
when  the  flow  of  the  blood  is  slackened,  thrombi  are  particularly 
likely  to  form,  because  these  ectases  favor  the  agglutination  of 
leucocytes  and  plaques  from  which  arises  the  inception  of  the 
thrombotic  process   (stagnation  tiirombosis) . 


134 


Disturbances  of  Circulation. 


3.  Alterations  of  the  lining  of  the  vascular  wall :  Lesions  of 
the  vascular  intima  resulting  in  the  destruction  of  the  endothelium 
and  thus  causing  a  loss  of  the  natural  smoothness  of  its  surface  give 
opportunity  for  adhesion  of  platelets  and  white  blood  corpuscles  to 
the  roughened  surfaces  and  give  origin  to  thrombus  formation 
{adhesion  thrombosis).  In  lacerations,  incised  and  puncture 
wounds  as  well  as  contusions  of  the  vessels,  thrombi  invariably 
form,  an  important  feature  in  wounds  both  as  regards  healing  and 
preservation  of  life,  the  clot  formation  gradually  closing  the 
rent  in  continuity  of  the  vessel  and  checking  the  loss  of  blood. 
Thrombosis  also  takes  place  in  case  of  vascular  changes  caused  bv 
bacterial  invasion,  parasites,  perforating  neoplasms,  and  in  vessels 
in  the  neighborhood  of  active  inflammatory  lesions,  as  upon  the 
valves  in  case  of  endocarditis,  in  the  vessels  of  the  lungs  in  pneu- 


Fig.  5. 
Thrombosis    in    a    cavernous  angioma  of  tiie  liver  of  a  cow. 


monia,  in  parasitism  of  the  arteries  by  strongylits  annatus,  in  case 
of  invasion  of  pyogenic  bacteria  in  the  umbilical  vein,  etc. 

As  a  rule  two  or  three  conditions  favoring  thrombus  formation 
cooperate  to  cause  it ;  thus  when  a  thrombus  is  formed  after 
bacterial  invasion  of  a  vessel,  it  is  partly  the  result  of  special 
ferment  production,  partly  due  to  injury  of  the  intima. 

The  composition  of  thrombi  varies  with  the  rapidity  of  forma- 
tion and  the  causes  of  production.  Those  rapidly  formed  and 
caused  by  special  elaboration  of  ferment  are  often  quite  like  the 
clots  of  external  haemorrhage,  homogeneous  and  of  a  dark  red  color 
throughout,  being  made  up  mainly  of  fibrin  and  red  blood  corpuscles 
{homogeneous  thrombi)  ;  microscopically  the  fibrin  forms  an  intri- 
cate reticulum  of  delicate  threads  in  a  radiating  or  stellate  form 
around  ihe  disintegrating  leucocytes  which  furnish  the  fibrin  fer- 
ment (coagulation  centers  of  Al.  Schmidt  and  Ribbert).     Stratified 


T/iroinbosis.  135 

or  layered  thrombi,  usually  forminf;'  upon  a  limited  area  of  the  vessel 
wall,  Itegin  b}'  the  adhesion  of  white  blood  corpuscles  and  plaques 
to  the  altered  part  of  the  vessel  wall  and  their  accumulation  at  such 
site ;  upon  this  basis  fibrin  is  deposited  in  layers  of  varying  extent 
and  quantity,  enclosing  the  corpuscular  elements  of  the  blood  in  its 
structure.  The  arrangement  of  this  coagulum  is  often  such  that 
in  microscopic  sections  the  framework  of  the  thrombus  may  be 
observed  to  be  formed  of  wavy  trabecula  of  granular  substance 
made  up  of  blood  platelets  (Ribbert)  ;  these  bands  always  sur- 
rounded by  a  broad  zone  of  leucocytes  and  between  them  the  net- 
work of  fibrin  fibrils  spread  out  with  the  red  corpuscles  included 
in  the  reticulum  (Ribbert).  Corresponding"  with  the  greater  or 
smaller  amount  of  the  constituent  fibrin  and  cells  and  the  types  of 
formation  described,  the  general  appearance  of  thrombi  and  their 
color  and  consistence  vary.  There  may  be  distinguished  the  follow- 
ing varieties  from  this  viewpoint: 

I.  Red  thrombi,  showing  a  homogeneous,  blood  red,  gelatinous 
mass,  similar  to  the  post-mortem  clots    ["'currant-jelly  thrombi"]. 

I.  White  and  grayish-red  thrombi,  reminding  one  of  bacon-fat 
or  spinal-cord  tissue  or  minced  meat,  not  transparent,  but  opaque, 
dull,  of  the  consistence  of  soft  rubber  or  cooked  minced  meat. 

3.  Mixed  and  stratified  thrombi,  made  up  of  alternating  layers 
of  red  and  white  coagulum,  well  seen  in  cross-section,  often  arranged 
concentrically  like  the  tunics  of  an  onion  and  separable  like  the 
leaves  of  a  book  from  each  other.  The  reason  for  this  lamination 
and  alternating  arrangement  is  to  be  found  in  the  fact  that  new 
layers  are  not  being  continuous!}-  formed  upon  the  primary  clot 
but  are  deposited  at  intervals,  the  older  layers  thus  attaining  a  cer- 
tain degree  of  firmness,  and  the  new  ones  not  adhering  so  closely 
to  the  previously  formed  strata  and  remaining  easily  separable  from 
them.  Where  such  mode  of  increment  is  frequently  repeated  the 
thrombus  may  exhibit  quite  a  number  of  layers.  The  surface  of 
these  thrombi  may  be  either  smooth  or  uneven,  often  marked  by 
ridges  or  ribs ;  the  latter  peculiarity  is  due  to  the  trabecula  of  blood 
platelets  and  leucocytes  extending  to  the  surface  and  forming  ledge- 
like projections  with  trough-like  depressions  between  them  (similar 
to  the  wavy  deposit  of  river  sand,  and  according  to  Zahn  probably 
produced  by  the  wave-like  motion  of  the  blood).  [Such  appearance 
may  be  produced,  too,  by  the  uneven  contraction  of  the  mass,  the 
shrinkage  being  most  marked  in  the  fibrinous  network  lying  between 
the  coarser  plaque-trabecula.] 


136  Disturhances  of  Circulation. 

The  clots  appearing  at  the  beginning  of  thrombosis  are  known 
as  primary  (autochthonous)  thrombi;  the  coagula  subsequently 
deposited  upon  them  as  secondary  or  consecutive  thrombi.  The 
former  are  more  or  less  firmly  attached  to  the  vessel  wall  {parietal 
thrombi)  ;  the  latter  usually  lie  free  in  the  lumen  as  cylindrical 
plugs  with  conical  or  rounded  ends.  The  thrombus  increases  prin- 
cipally in  the  direction  of  the  blood  stream,  in  the  arteries  toward 
the  periphery  of  the  circulation,  in  the  vei,ns  centripetally.  The 
length  may  be  quite  considerable,  as  in  those  extending  from  the 
veins  in  the  neck  down  into  the  heart,  or  from  the  aorta  at  the 
level  of  the  renal  artery  down  into  the  arteries  of  the  popliteal  space 
and  leg  with  or  without  (discontinuous)  continuity.  The  thickness 
depends  upon  the  calibre  of  the  blood  vessel ;  parietal  clots  are  at 
first  flat,  marked  with  wavy  ridges,  villous,  or  in  the  pockets  of  the 
valves  of  the  veins  may  form  smoothl}'  rounded  plugs  (zalviilar 
thrombi)  ;  with  growth  the  thrombus  ma}-  cause  complete  occlusion 
of  the  vascular  lumen  (total  occluding  thrombi).  In  arteries 
thrombi  are  usually  smaller  than  the  calibre  of  the  relaxed  vessel, 
being  compressed  by  the  contraction  of  the  i)ulsating  vessel  wall. 
In  aneurisms  and  in  the  cardiac  chambers  there  occur  huge  irregular 
nodulated  thrombi,  sometimes  are  large  as  the  fist.  Thrombi  in 
the  course  of  time  undergo  a  number  of  changes  (metamorphoses) 
as  well  might  be  supposed.  They  are  but  dead  masses  made  up  of 
coagulated  and  necrotic  elements  and  may  shrink,  becoming  firmer, 
drier  and  smaller;  such  changes  depending  upon  changes  in  the 
structure  with  homogenization  of  the  fibrin  and  plaques  and  upon 
pressure  exerted  by  the  walls  of  the  vessels.  In  clots  which  have 
undergone  such  changes  there  may  occasionally  take  place  a  calcare- 
ous deposit  (vein  stones,  phleboliths).  As  a  result  of  such  shrink- 
age the  vascular  lumen  may  again  become  partially  permeable  to  the 
blood.  [The  diminution  in  size  of  an  old  clot  depends  in  an  im- 
portant degree  upon  the  shrinkage  of  its  own  fibrinous  network ; 
this  may  be  easily  noted  in  the  shrinkage  which  takes  place  in  any 
clot  outside  the  body,  with  the  separation  of  the  serum  originally 
present  in  the  coagulum,  the  question  of  compression  by  the  vessel 
walls  being  in  such  case  entirely  eliminated.]  The  most  common 
change  consists  in  a  softening  of  the  thrombus,  the  clot  being  trans- 
formed by  fatty  degeneration  of  its  leucocytes  [and  liquefaction  of 
any  of  its  elements]  into  a  gray  or  grayish-red  mass  of  pultaceous 
consistence  somewhat  like  minced  meat.  This  change  may  be  a 
favoring   circumstance,    but    is    open   to    serious   consequences.     In 


Thrombosis. 


m 


case  the  substance  is  broken  up  into  a  tinely  granular  falty  material 
this  may  be  taken  up  by  the  blood  current  and  washed  away  and 
the  lumen  of  the  vessel  may  thus  be 
again  established,  or  through  the  soft- 
ened clot  the  blood  stream  may  some- 
times force  one  or  more  passageways 
(canalization  of  the  thrombus). 
Should,  however,  larger  fragments, 
as  a  result  of  the  degenerative 
changes,  bd  loosened  from  the  coagu- 
lum  and  swept  onward  by  the  current 
of  blood  they  may  find  lodgment  in 
some  other  part  of  the  circulator}'  ap- 
paratus and  give  rise  to  embolism. 

A  thrombus  acts  as  a  foreign 
body  u])on  the  living  vessel  walls 
with  which  it  is  in  contact ;  and  its 
characteristic  properties  excite  an  in- 
vasion by  leucocytes  and  phagocytic 
activity.  The  latter  may,  as  is  uni- 
formly true  in  case  of  small  traumatic 
thrombi,  bring  about  complete  ab- 
sorption of  the  clot,  Coincidently 
there  is  established  an  inflammation 
of  the  vessel  wall  w'ith  fibroplastic 
and  angioplastic  proliferation,  result- 
ing in  the  formation  of  embryonic 
connective  tissue  and  vascular  buds 
from  the  endothelium  and  vasa  vaso- 
rum  and  their  penetration  into  the 
thrombus.  These  proliferating  ele- 
ments replace  in  time  more  or  less 
completely  the  clot  substance.  In 
case  the  thrombus  were  a  parietal 
one,  occupying  onl\-  one  side  of  the 
vessel  wall,  as  after  venesection,  after 
removal  of  the  clot  the  connective 
tissue  contracts  and  shrinks  into  a 
flat  scar  or  mere  thickening  of  the 
wall.  \Micre  the  thrombus  occupies  the  whole  lumen  the 
embryonic    tissue    develops    about    it,    and    in    its    growth    pene- 


a 


r^ 


Fig.    6. 

Schematic  section  of  a  throm- 
bosed vein;  somewhat  en- 
larged.     (After  Thoma.  I 


138 


Disturbances  of  Circulation. 


trates  the  mass ;  and  in  the  site  of  the  clot  there  is  formed  a 
mass  of  connective  tissue.  These  changes  are  known  under  the 
term  organization  of  the  thrombus.  The  vessel  in  the  situation  in 
question  is  converted  into  a  solid  cord,  its  lumen  completely 
obliterated ;  and  as  a  result  of  shrinkage  of  the  newly  formed  con- 
nective tissue  the  part  eventually  may  be  seen  as  a  thin  string-like 
obliterated   section   of  the   vascular  tube.     Now   and   again   spaces 


Fig.   7. 

Embolism  of  branches  of  the  pulmonary  artery  ;  the  superior  embolus  almost  com- 
pletely adherins;  to  the  vessel  walls  and  shmmken.  Somewhat  reduced. 
(After  Thoma.) 


are  left  in  the  connective  tissue,  however,  through  which  blood  in 
some  degree  may  pass. 

If  a  thrombus  or  a  portion  of  a  thrombus  should  break  away,  it 
is  carried  forward  with  the  blood  current  and  must  find  lodgment 
at  some  point  where  the  calibre  of  the  artery  is  less  than  the  diam- 
eter of  the  floating  mass.  The  latter  is  then  spoken  of  as  an 
embolus,  and  the  process  as  embolism.  Detachment  is  especially 
likely  to  take  place  in  connection  with  softening  of  a  thrombus,  in 
Vv  hich   process  the  clot  may  easily  crumble  :  however,  even  entire 


Embolism.  1.^9 

thrombi,  no  matter  whether  loosel\-  or  tirmly  attached,  may  some- 
times accidentally  be  torn  loose  by  external  force  exerted  upon  the 
vessel  through  movements  occasioning  twisting  of  the  vessels  or 
increase  of  blood  pressure.  At  the  points  of  branching  of  the 
vascular  tubes  it  may  happen  that  a  thrombus  or  embolus  may 
strike  upon  the  dividing  angle  and  here  again  be  broken  into  frag- 
ments or  may  remain  fixed  at  the  point  of  division.  It  is  quite 
likely  that  an  unusually  long,  flexible  and  tough  thrombus  may  so 
lodge  at  these  places  of  division  as  to  extend  into  both  branches 
of  the  vessel,  riding  as  if  in  a  saddle  (riding  embolus).  A  long 
cvlindrical.  flexible  thrombus  may,  moreover,  be  thrown  into  folds, 
twisted  in  serpentine  fashion  and  compressed  into  a  mass  by  the 
force  of  the  blood  stream. 

Although  an  embolus  displaced  from  its  original  site  is  forced 
into  a  relatively  narrow  portion  of  the  vessel,  it  does  not  neces- 
sarily at  once  completely  occlude  the  lumen,  since  as  a  broken 
fragment  of  a  thrombus  it  need  not  retain  the  cylindrical  shape 
of  the  vascular  tube,  but  may  well  be  of  irregular  and  angular 
outline.  Such  emboli,  particularly  when  of  the  riding  type,  are 
apt  to  leave  room  free  about  them  for  the  passage  of  blood.  Cyl- 
indrical or  round  emboli  are  comparatively  easily  forced  into  the 
vascular  lumen  and  give  rise  to  complete  obstruction.  An  embolus 
which  has  become  lodged  tends  to  further  enlargement,  either  by 
the  massive  coagulation  of  the  stagnant  column  of  blood  adjacent 
or  by  the  deposition  of  thrombotic  layers.  Sooner  or  later  this 
leads  to  complete  obstruction  of  the  vessel.  In  these  cases  it  is 
often  difficult  to  determine  whether  there  was  primary  thrombosis 
or  whether  an  embolism  formed  the  nucleus  of  the  blood  clot, 
which,  from  the  formation  of  new  layers,  comes  to  completely  fill 
out  the  lumen  of  the  vessel,  and  the  original  embolus  may,  more- 
over, have  been  very  small,  and  entirely  hidden  by  the  further 
depositions. 

The  course  traversed  by  an  embolus  is  determined  by  cir- 
culatory circumstances.  An  embolus  carried  from  the  veins  must 
always  pass  into  the  right  heart  and  thence  into  the  pulmonary 
arteries;  it  may,  however,  adhere  to  the  auriculo-vcntricular  valve 
leaflets  in  the  heart.  Its  convection  to  the  heart  is  easy,  the  veins 
becoming  wider  and  wider  from  the  periphery  centrally  to  the 
venje  cavse.  If  therefore  a  fragment  become  loosened  from  a 
thrombus  in  veins  of  the  foot,  thymid.  uterus  or  liver  it  would 
be  swept  by  a  continually  widening  current  to  the  heart.     Commg 


140 


Disturbances  of  Circulation. 


from  the  intestine,  stomach  or  spleen  in  the  portal  vein,  emboli 
must  lodge  in  the  liver ;  embolism  of  the  latter  organ  arising  also 
from  the  umbilical  vein,  inasmuch  as  there  is  no  direct  communica- 


Aorta 


Niere 


cava  post. 


Fig.   8. 

Schematic  representation  of  the  circulation  with  fragments  of  thrombi  at  different 
positions  (cf.  text).  Lungencapillaren.  pulmonary  capillaries;  Linke  Herzk., 
left  cardiac  ventricle :  Rechte  Herzkammer.  right  cardiac  ventricle ;  Magen, 
stomach  ;  Milz,  spleen  :  Darm,  intestine  ;  Nabel.  umbilicus  ;  Leber,  liver  ;  Niere, 
kidney. 


Embolism. 


141 


tion  of  the  portal  and  umbilical  veins  with  the  vena  cava,  their 
blood  passin.c^  into  the  fine  meshed  capillary  network  of  the  portal 
vein  within  the  liver  substance.  (In  calves,  however,  where  the 
ductus  Arantii  forms  a  direct  passage  between  the  uml)ilical  vein 
and  the  vena  cava  the  lung  may  stand  equal  chance  of  embolism 


haemo7rhof{ 
dalis\ 


Einige 
'Dmndarmd.ste 


coeci 


Fig.   9. 

Thrombosis    of    the    colic   arteries   of   a  horse:  ;i  riding  emljolus  in  arleri:i  cceci. 

Vordere     Gekroswurzel,     anterior     mesenteric  t runic ;      einige      diinndr.rmaste, 
branches   to    small    intestine. 


from  the  last  named  source.)  Emboli  from  the  left  heart,  from  the 
lungs  (pulmonary  veins),  entering  the  aorta  and  arterial  tree  always 
find  their  way  into  the  peripheral  arterial  branches,  as  from  the 
anterior  portion  of  the  aorta  into  the  brain,  from  the  posterior 
aorta  into  the  kidneys,  pelvic  arteries,  etc.,  from  the  mesenteric 
trunk  into  the  arteries  of  the  intestines.     As  a  rule  blgod.  dots  are 


142  Disturbances  of  Circulation. 

not  so  minute  that  they  can  be  carried  from  the  arteries  through 
the  capillaries  into  the  veins,  for  which  reason  such  emboli  from 
the  pulmonary  arteries  become  fixed  in  their  branches,  that  is,  in 
the  lungs ;  other  types  of  emboli,  however,  as  minute  animal 
parasites  or  bacteria,  may  traverse  a  capillary  area  and  may  there- 
fore pass  from  the  greater  into  the  lesser  circulation  and  in  turn 
arrive  again  in  the  greater. 

In  ver}'  rare  instances  in  human  beings,  where  there  is  a  patulous 
foramen  ovale,  emboli  have  been  encountered  in  tlie  aorta  and  its  branches 
which  did  not  originate  in  the  left  heart  or  lungs,  but  which  passed 
directly  from  the  right  into  the  left  heart  through  the  patulous  opening. 
When  first  seen,  before  the  condition  of  the  foramen  ovale  has  been 
noticed,  the  existence  of  such  embolism  seems  inexplicable  and  confusing, 
for  which  reason  such  an  occurrence  is  spoken  of  as  paradoxical  embolism. 
In  addition,  it  should  be  mentioned  that  there  is  a  possibility  of  retrograde 
embolism  of  embolic  substances  in  the  veins.  This,  according  to  Ribbert, 
may  be  explained  on  the  supposition  that  clots  or  emboli  of  any  type 
which  happen  to  lie  close  to  the  inner  surface  of  a  comparatively  large 
vein  are  always  subject  to  slight  backward  repression  by  recurrent  waves 
of  the  venous  blood  (venous  pulsation  in  passive  congestion),  somewhat 
as  at  the  shore  the  surging  wave  carries  back  with  it  a  floating  log  into 
the  sea.  If  the  venous  current  to  the  heart  be  weak^  as  in  congestive 
states,  it  may  not  carry  the  embolus  forward  with  it,  while  the  more 
powerful  backward  impulse  forces  it  gradually  back  toward  the  periphery 
to  the  capillaries.  [This  is  well  seen  sometimes  in  cases  of  valvular 
insufBciency  and   regurgitation.] 

The  results  of  thrombosis  and  enibolisni  vary  with  the  vascular 
conditions,  the  size  and  nature  of  the  obstructive  substance  and  the 
relative  importance  of  the  afifected  organ.  In  part  they  are  purely 
mechanical,  depending  upon  the  degree  of  narrowing  or  obstruction 
of  the  lumen  occasioned  by  the  process  and  the  consequent  dis- 
turbance of  circulation ;  in  part  the  results  may  be  specific  (pe- 
culiar), the  nature  of  the  thrombus  involving  some  special  prop- 
erties (as  pyogenic  or  putrefactive  agencies,  or  tumor  forming 
elements).  Thrombosis  of  arteries  occasions  primarily  an  anaemia 
of  the  organ  or  area  supplied  by  the  artery  afifected.  This  anrcmia 
in  vital  organs  like  the  brain  or  heart  or  lungs  necessarily  imme- 
diately induces  disturbances  of  function  dangerous  to  life  itself 
(fainting,  cessation  of  cardiac  action,  phenomena  of  asphyxia),  if 
an  important  artery  be  involved  and  quick  compensation  by  anasto- 
motic blood  supply  is  impossible.  In  case,  however,  branches  of 
the  occluded  or  obstructed  artery  are  so  connected  with  other 
adjacent  arteries  that  a  sufficient  amount  of  blood  is  supplied  to 


Embolism. 


143 


the  organ  by  these  anastomoses  or  collateral  communications,  the 
anaemia  is  likely  to  be  only  of  short  duration  and  without  func- 
tional disturbance.  In  many  organs  such  collateral  paths  arc  very 
abundant,  and  in  some,  as  in  the  muscles  and  hmgs.  Ihey  are  so 
numerous  and  of  such  calibre  that  sufficient  blood  is  transmitted  to 
the  blocked  area  of  the  artery  by  the  ordinary  collateral  circula- 
tion witliout  any  special  effect.     The  blood  which  previously  tra- 


Fig.  10. 

Femoral  artery  of  a  large  dog,  injected 
three  months  after  ligation.  (After 
Porta.) 


Fig.    11. 

Carotid  artery  of 
a  goat,  injected 
thirty -five  months 
a  f  t  e  r  ligation. 
(.\ftpr   Torta.) 


versed  the  occluded  vessel  is  of  course  distributed  throughout  the 
permeable  branches  arising  proximal  to  the  site  of  obstruction 
and  driven  into  these  by  the  arterial  pressure.  The  blood  pressure 
in  these  collateral  paths  must  therefore  be  somewhat  raised,  for 
which  reason,  as  well  as  from  the  probability  that  the  ansemic  area 
actually  sucks  in  the  blood  from  these  paths,  the  blood  in  the 
collaterals  flows  with  increased  rapidity.  This  excess  of  pressure 
also  determines  an  additional!   dilatation  of  the  collateral  vessels, 


144 


Disturbances  of  Circulation. 


corresponding  at  first  merely  to  their  distensibility  ;  but  after  the 
dilatation  has  persisted  for  a  time  there  also  occurs  a  proliferation 
of  the  cells  of  the  vessel  walls  in  consequence  of  the  altered  con- 
ditions of  tension,  not  only  causing  narrow  arteries  to  assume 
wide  calibre,  but  changing  capillary  vessels  into  arteries.  It  is 
in  this  manner  that  a  tissue  whose  principal  artery  has  been  ligated 
or  occluded  by  thrombosis  has  its  blood  supply  restored.  The 
development  of  collateral  circulation,  however,  requires  time  before 
complete  compensation  is  attained ;  and  should  the  existing  anasto- 


Fig.   12. 

Embolism    of  an   artery    with    congestion   of 
its  two  vense  comites. 


Fig.   13. 

Supply    by    anastomotic    channels. 


motic  channels  be  very  small,  few  or  entirely  absent,  the  tissue  must 
in  the  interim  sufifer  from  the  circulatory  loss,  be  moi'e  or  less  com- 
pletely deprived  of  its  nutriment  and  perish.  This  is  particularly 
true  when  there  are  absolutely  no  arterial  anastomoses.  Arteries 
which  possess  no  communicating  channels  with  neighboring  arterial 
areas  are  commonly  known  as  end-arteries,  following  Cohnheim. 
Parts  of  organs  supplied  with  no  arterial  anastomoses  have  of 
course  capillary  communications  with  the  adjacent  tissues,  but  the 
small  amount  of  blood  which  passes  through  these  minute  channels 
is  often  insufificient  to  maintain  the  nutrition  of  the  area  deprived 
of  its  arterial    supply ;   only   in    case   of   very   small   areas   is  the 


Infarction.  145 

capillary  supply  sufficient  for  this  purpose.  Moreover  it  may  hap- 
pen that  it  is  not  one  single  artery  that  is  blocked,  but  that  at  the 
same  time  its  anastomosing  vessels  are  also  occluded,  under  which 
circumstances  there  necessarily  result  circulatory  disturbances  hav- 
ing serious  consequences.  The  area  which  is  deprived  of  its  blood 
supply  loses  its  blood  color,  and  assumes  a  paler  and  drier  appear- 
ance than  the  surrounding  tissue;  the  blood  remaining  in  it  be- 
coming decolorized  because  its  hccmoglobin  is  dissolved,  disin- 
tegrated or  dispersed  by  diffusion,  and  the  anaemic  tissue,  in  which, 
too,  the  lymph  is  stagnant  and  coagulates,  undergoing  regressive 
metamorphoses.  Such  an  ansmic  and  dead  area  is  known  as  an 
anccmic  infarct. 

A  tissue  which  is  thus  cut  out  of  the  circulation  and 
deprived  of  its  arterial  blood  supply  is  not  necessarily  anaemic 
but  on  the  contrary  may  be  the  scat  of  a  distinctly  pathological 
engorgement  as  a  result  of  regurgitation  of  blood  from  the  veins. 
Particularly  where  the  veins  of  the  part  whose  arterial  supply 
has  been  occluded  anastornose  with  adjacent  veins,  the  blood,  which 
in  the  latter  vessels  is  under  a  certain  amount  of  pressure,  flows 
over  into  the  former  and  back  into  the  anaemic  network  of  capil- 
laries;  just  as  the  water  from  a  brook  moves  back  into  the  side 
ditches  of  a  stream  if  these  have  no  fall.  There  is  no  force  from 
the  arteries  in  such  a  site  capable  of  driving  the  blood  through  the 
afifected  area  and  the  capillaries  in  which  the  venous  blood  collects 
become  distended  and  their  walls  flaccid  and  permeable  from  the 
lack  of  normal  bathing  with  flowing  blood.  The  venous  blood 
thus  stagnating  in  the  capillaries  partly  leaks  through  their  w^alls, 
partly  undergoes  coagulation;  and  the  whole  area  thus  engorged 
with  blood  assumes  a  dark  red  hue.  Such  an  area  is  spoken  of  as 
a  hccmorrhagic  infarct  (infarcire,  to  stop  up).  [Others  would 
refuse  the  importance  attached  by  the  author  to  the  above  idea  of 
a  venous  regurgitation  giving  rise  to  the  engorgement  of  the  in- 
farcted  area  with  blood.  Anastomotic  communications  are  usu- 
ally more  numerous  and  free  between  veins  than  between  arteries ; 
and  if  this  be  true  and  the  author's  views  correct,  anremic  infarcts 
should  be  the  exception  rather  than  of  as  common  occurrence  as 
they  actually  appear.  If  venous  reflux  were  as  easy  as  supposed 
by  the  older  adherents  of  this  theory,  anaemic  infarcts  should  be 
practically  unknown.  From  the  editor's  viewpoint  the  process  is 
more  easily  understood  if  we  accept  the  belief,  which  seems  rea- 
sonable, that  there  are  no  true  end-arteries  and  that  there  are  al- 


146  Disfurboiiccs  of  Circulation. 

ways  some  small  anastomotic  channels  between  adjacent  terminal 
arterial  areas.  Through  such  anastomoses,  inappreciable  under 
normal  conditions  but  distended  by  the  collateral  rise  of  blood 
pressure  when  the  embolism  diverts  the  blood  into  the  surround- 
ing areas  of  distribution,  the  blood  enters  the  infarct.  The  ques- 
tion whether  in  any  given  case  an  embolism  should  cause  an  anaemic 
or  a  hemorrhagic  type  of  infarct  is  largely  determined  by  the 
texture  of  the  tissue  in  which  the  lesion  occurs,  anaemic  infarcts 
being  met  in  relatively  firm  tissues  as  in  the  kidneys,  and  haemor- 
rhagic  in  looser  structures  as  in  the  lungs.  The  explanation  of 
such  distribution  is  not  entirely  clear  but  probably  rests  in  the 
facility  afforded  by  the  tissues  at  the  border  of  the  infarct  for  dis- 
tension of  the  capillary  anastomotic  channels  entering  the  infarcted 
area.  Naturally  the  looser  the  texture,  the  greater  the  ease  of 
such  dilatation.  It  should  however  be  realized  that  the  collateral 
congestion  existing  along  the  border  of  the  infarct  is  productive  of 
swelling  and  of  pressure  upon  the  periphery  of  the  infarct. 
Granted  a  fairly  firm  structure,  such  pressure  should  compress  the 
very  channels  of  ingress  into  the  interior  of  the  infarct  which  are 
here  supposed  to  give  opportunity  for  the  entrance  of  blood :  and 
in  such  instances  the  part  occluded  should  remain  anaemic.  If. 
however,  the  tissue  be.  loose  in  texture  such  compression  cannot  be 
of  sufficient  importance  to  occasion  the  interference  with  these 
anastomotic  channels  just  suggested  ;  and  here  the  blood  may  by 
such  paths  enter  the  area  from  the  zone  of  collateral  hyperaemia 
and  give  rise  to  the  appearance  of  a  haemorrhagic  infarct.  In- 
farcts of  the  lung  are  usually  haemorrhagic  in  type  in  conformity 
with  the  natural  looseness  of  this  tissue ;  but  the  writer  recalls 
a  recent  case  of  an  anaemic  infarct  of  a  collapsed  lung,  bear- 
ing out  the  above  theory.  There  is  no  objection  to  the  author's 
views  in  so  far  as  entrance  of  blood  to  the  infarct  through  venous 
anastomoses  may  constitute  a  part  of  the  process ;  but  to  the 
writer's  mind  it  is  excessive  to  suppose  that  this  factor  with  reflux 
of  blood  into  and  through  the  venules  and  capillaries  irom  the 
veins  is  the  sole  explanation  of  the  phenomenon ;  and  in  his  opinion 
both  arterial  and  venous  anastomoses  may  contribute,  regulated 
however  by  the  factors  of  border  swelling,  texture  of  tissue  and 
pressure,  to  determine  to  what  degree  the  entrance  of  blood  may 
be   possible] . 

Microscopically  a  haemorrhagic  infarct  exhibits  the  capillaries  of 
the  part  turgid  with  blood  and  the  lymph  spaces  and  all  the  tissues 


Iiifarcfioii.  T47 

infiltrated  with  lucniorrliagic  ci'lusiun.  Ju  larj^e  infarcts  the  con- 
gestive reflux  of  venous  blood  is  often  restricted  to  the  periphery 
of  the  area  alone,  the  central  portions  remaining  anaemic  and  hav- 
ing therefore  only  a  red  areola. 

Infarcts  as  a  rule  are  conical  in  shape,  the  apex  of  the  cone 
at  the  position  of  arterial  occlusion,  the  expansion  from  this  point 
corresponding  with  the  branching  of  the  artery.  From  fusion  of 
closely  situated  infarcts  or  in  those  of  flat  organs  like  the  wall  of 
the  intestinal  canal,  the  conical  shape  may  be  indefinite  and  the 
outlines  suggestive  of  a  map.  Hasmorrhagic  as  well  as  anaemic  in- 
farcts occasion  destruction  of  the  tissue,  the  circulation  being  en- 


&i^  ,^- 


•«• 


Fig.    14. 
Conical  liaemorrhagic  infarct.s   in  a  portion  of   the  Ividney  of  a   cow. 

tirely  ended  in  the  area  involved  ;  the  tissue  with  all  the  blood  which 
has  engorged  it  being  reduced  to  a  mass  of  coagulated  necrotic  ma- 
terial. Such  an  area  excites  an  inflammation  in  the  surrounding 
tissue,  to  the  formation  of  an  actual  inflammatory  zone  of  demarca- 
tion ;  a  wall  of  leucocytes  collecting  around  the  area  of  coagulated 
material,  fibroblastic  and  angioplastic  cells  from  the  surrounding 
healthy  structure  penetrating  the  infarct,  whether  it  be  an.xmic  or 
hsemorrhagic,  the  blood  and  disintegrating  tissue  of  the  infarct 
being  removed  by  phagocytosis,  and  the  site  of  the  infarct  being 
eventually  occupied  by  a  mass  of  contracting  connective  tissue 
(infarct  scar).  Such  cicatrices  are  quite  common  in  the  kidneys 
(cicatricial  kidneys).  When  either  an  anremic  or  h?emorrhagic 
infarct  is  related  to  some  surface  infected  with  bacteria  these  in- 


148 


Distiirhanccs  of  Circulation. 


variably  invade  every  part  of  its  tissue,  causing  its  destruction  by 
moist  gangrene,  as  is  regularly  seen  in  such  lesions  of  the  in- 
testine (septic  destruction  of  the  intestine). 

Thrombi,  developing  in  the  veins  so  as  to  cause  their  occlusion, 
of  necessity  interfere  with  the  passage  of  the  venous  blood  from 
the  peripher}^,  and  of  course  give  rise  to  passive  congestion.  The 
duration  and  termination  of  such  cases  also  depend  upon  the 
presence  or  absence  of  proper  collateral  communications.  In  case 
of  a  partial  or  complete  occlusion  of  unpaired  venous  trunks  (vena 


Fig-.    15. 

Cicatricial    shrinliage    after    embolism     (hfemoi-rhagic    infarcts)     of    the    kidney 

of  a  hog. 


cava,  portal  vein)  or  in  case  of  synchronous  thrombosis  of  a  num- 
ber of  venous  tributaries  (veins  of  the  lung)  a  serious  passive  con- 
gestion is  occasioned,  with  stasis  of  the  blood  column,  hremorrhagic 
infiltrations  or  congestive  transudations.  Should  there  be  a  num- 
ber of  collateral  branches  of  sufficient  calibre  the  stagnation  of 
Wood  will  extend  from  the  point  of  occlusion  only  to  the  first 
collateral  branch,  and  the  blood  wull  pass  without  difficulty  by  the 
collateral  route  to  the  heart ;  should  the  anastomotic  passageways 
be  narrow  they  may  become  dilated  by  the  pressure  of  the  ob- 
structed blood  and  the  tissue  be  gradually  relieved  of  its  congestion, 
provided  the  degree  of  dilatation  will  accommodate  the  blood  ac- 
cumulated in  the  various  venous  channels  of  the  structure.  A'ery 
small  veins  and  the  capillaries  everywhere  in  the  part  may  be  so 
distended  as  to  serve  the   purposes  of  drainage,  thus  conducting 


Embolism.  149 

the  blood  by  a  round-about  way  into  one  of  the  venae  cavee.  Clots 
and  fragments  of  clots  from  the  capillaries  and  veins  pass  as 
emboli  to  the  right  heart  and  thence  to  the  lungs. 

In  the  same  way  as  clots,  a  variety  of  substances  may,  if  once 
they  have  gained  entrance  to  the  blood,  be  carried  along  by  the 
current  and  give  rise  to  embolism.  Virchow  and  Cohnheim,  whose 
studies  were  fundamental  to  our  kucnvledge  of  the  embolic  process, 
showed  that  small  balls  of  wax  introduced  into  the  blood  vessels 
are  carried  along  by  the  current,  lodge  in  some  relatively  narrower 
place  in  the  vascular  tube,  and  give  rise  to  all  the  mechanical  con- 
sequences of  embolism.  Sometimes  parasitic  worms  which  have 
succeeded  in  making  their  way  from  the  intestine  into  the  radicles 
of  the  portal  vein  are  conveyed  with  the  portal  blood  into  the  liver 
and  may  be  carried  thence  onward  as  emboli  to  the  heart  and  lungs ; 
very  minute  animal  parasites,  as  the  rounded  oncospheres,  measur- 
ing only  20  to  40  micromillimeters  in  diameter,  and  larval  tricliina", 
may  slip  through  the  capillaries  of  the  pulmonary  circulation,  often 
measuring  o.i  mm.  in  diameter,  and  thus  gaining  access  to  the 
arterial  stream  be  carried  to  any  of  the  organs.  It  may  be  easily 
appreciated  from  this  wliy  the  liver  and  lungs  are  the  most 
common  sites  for  echinococcus  cysts ;  and  the  embolic  mode  of  dis- 
tribution of  the  parasites  is  recognized  from  their  usual  wide  dis- 
semination throughout  the  whole  organ.  Of  the  larger  parasites 
which  the  blood  may  aid  in  distributing,  liver  lUikes  deserve  special 
mention ;  these  sometimes  in  their  migrations  in  the  hepatic  par- 
enchyma penetrate  into  the  branches  of  the  hepatic  vein  and  may 
pass  with  the  blood  through  the  right  heart  into  the  lungs.  The 
mechanical  consequences  of  embolism  by  these  animal  parasites  are 
usually  of  little  importance  because  of  the  minute  size  of  the  bodies 
and  the  relative  certainty  of  sufficient  anastomotic  supply  to  the 
small  areas  affected ;  and  disturbances  are  only  occasioned  by 
pressure,  etc.,  in  case  the  invading  parasite  increases  in  size.  The 
larger  parasites  like  stroiii^ylus  annatus  are  capable  of  directly 
causing  the  same  mechanical  eft'ects  as  described  iii  connection 
with  blood  clots    (as  cerebral  embolism  with  infarction). 

The  entrance  of  air  and  of  dro])lets  of  fluid  fat  may  also  oc- 
casion circulatory  disturbances  in  a  jnirely  mechanical  manner,  in 
the  same  way  as  blood  clots.  Air  cuibolisui  is  of  rare  occurence 
and  is  met  with  in  operations  on  the  neck."  The  air  which  is 
drawn  by  the  suction  force  of  the  lieart  through  a  valvular  venesec- 

*Traumatk-  a^rrnmia  was  first  observed  in  the  horse  l>y  the  French  veterin- 
arian,   Verrier     (1806). 


150  Disturbances  of  Circulation. 

tion  wound  into  the  jugular  vein,  or  which  is  accidentally  intro- 
duced in  intravenous  injection,  becomes  mixed  with  the  blood  in 
the  form  of  bubbles  of  various  sizes.  In  case  of  healthy  animals 
with  normal  blood  pressure,  moderately  large  quantities  of  air  (5 
to  10  cubic  centimeters  in  dogs,  sheep,  horses)  injected  into  the 
jugular  vein  are  sometimes  born  without  harmful  results,  the  air 
disappearing  quite  rapidly  by  absorption  in  the  circulating  blood. 
In  animals .  with  low  pressure  and  a  tendency  to  accumulation  in 
the  right  heart  (as  after  operations  and  after  loss  of  blood  in 
parturition)  the  air  bubbles  are  apt  to  accumulate  in  the  right 
heart  and  form  a  large  elastic  air  cushion  which  is  not  forced 
onward  by  systole,  being  only  compressed  by  cardiac  contraction 
and  expanding  again  in  diastole.  In  consequence  the  blood  is 
dammed  back  in  the  right  heart,  and  there  results  a  marked  dilata- 
tion of  the  right  ventricle,  reaching  two  or  three  times  its  normal 
volume.  (Death  takes  place  from  the  cardiac  dilatation  and  suf- 
focation, the  blood  being  prevented  access  to  the  lungs.  Accord- 
ing to  Frangois  Franck  it  may  also  be  possible  that  some  of  the 
air  passes  through  the  lungs,  and,  traversing  the  left  heart  into 
the  coronary  arteries,  brings  about  embolic  occlusion  of  the  latter 
and  anaemia  of  the  myocardium.*) 

Fat  ciiibolism  is  usually  met  in  connection  with  severe  con- 
cussive  lesions  of  the  bone  marrow  (Ribbert).  The  occurrence  of 
fracture  of  a  bone  with  such  concussion  allows  lacerations  of  the 
delicate  walls  of  the  venous  capillaries  to  take  place,  after  which 
fat  droplets  from  the  fat  cells  abundantly  present  in  the  marrow 
may  pass  into  the  blood  (Ribbert).  Access  of  fat  into  the  blood 
may  also  be  thought  possible  from  the  liver  cells  in  case  of  con- 
tusion .of  this  organ,  its  cells  also  being  usuall\'  rich  in  fat  (Rib- 
bert). The  oil  droplets  are  first  carried  with  the  venous  blood  to 
the  lung,  where  they  lodge  in  the  small  arteries  and  capillaries, 
the  capillary  network  often  appearing  turgid  as  if  filled  with  a 
fatty  injection  mass.  From  the  occlusion  thus  brought  about 
haemorrhagic  infarcts  are  formed  in  the  lungs,  usually  a  transient 
condition  (may  be  proved  by  injecting  a  fat  emulsion  into  the 
jugular).  The  liquid  fat  may.  however,  pass  through  the  pulmon- 
ary capillaries  and  be  carried  on  into  the  left  heart,  whence  it  may 
be  conveyed  with  the  aortic  blood  into  the  cardiac  musculature 
(coronary  arteries),  the  renal  glomeruli,  or  the  brain  and  other 
organs.     The  fat  lodged  in  the  coronary  arteries,  just  as  any  other 

*Recueil  veier.      1903,    p.    370. 


Metastasis. 


i=;i 


emboli,  occasions  anaemic  degeneration  of  the  myocardium;  in  the 
brain  numerous  small  hccmorrhages  ;  and  in  ^uch  or  other  analogous 
manner  fat  embolism  may  prove  fatal. 

Sometimes  after  traumatic  lesions  of  the  tissues,  cells  are  simi- 
larly swept  into  the  blood,  as  giant  cells  from  the  marrow  or  liver 
cells,  and  lodge  in  the  pulmonary  capillaries  because  of  their  size. 
This  type  of  cellular  embolism  occasions  no  special  disturbance,  the 
occlusive  lesion  being  at  the  most  a  minute  one  and  the  cells  soon 
broken  up  or  removed  by  phagocytosis.  However,  the  entrance  of 
tumor  cells  or  pathogenic  bacteria  into  the  blood,  and  the  embolic 
transmission  of  such  bodies,  are  of  much  more  importance.  Their 
mechanical  effects  in  causing  complete  or  partial  occlusion  of  the 


Fij 


16. 


Fat    embolism    of    the    lung,    eight    days    after    fracture    of    the    leg.     Drawn    by 

Dr.    Ziesing;     X  -oO. 

The  capillary  network  of  the  alveolus  to  the  right  is  cholved  with  blood,  the 
lower  one  with  fat  and  the  artery  likewise  Just  above  the  latter  are  two 
air  bubbles  (showing  as  dark  rings)  and  several  droplets  of  fat  whicn  na\e 
escaped  from   it    (with  simple  d.irk  outline),      (.\fter   Perls.) 

vessels  are  of  minor  significance  because  of  their  minute  size  ;  but 
because  of  their  nature  they  induce  specific  changes,  the  process 
being  knowm  as  one  of  malignant  embolism  or  as  metastasis  (Merdo-rao-ij, 
displacement ) .  We  have  here  to  deal  with  substances  which  have 
already  given  rise  to  pathological  processes  in  some  part  of  the 
system,  and  which  are  now,  by  being  transported  by  the  blood  into 
new  situations  in  the  body,  inducing  the  same  disturbances  in  the 
latter.     Emboli  composed  of  tumor  cells  originate  from  autoblas- 


152  Disturbances  of  Circulation. 

tomata  (neoplasms,  tumors)  whose  cells  in  the  growth  of  the 
mass  are  penetrating  the  walls  of  the  blood  vessels  and,  picked  up 
5y  the  blood  flowing  by,  are  carried  along  with  the  stream.  Wher- 
ever they  lodge  a  new  autoblastic  growth  develops  from  the  multi- 
plication of  the  displaced  cells,  which  retain  their  power  of  growth. 
Since  usually  it  is  not  one  single  cell  which  is  thus  swept  from  the 
primary  site,  but  whole  groups  of  cells  being  loosened  and 
separated  from  each  other  in  the  circulating  blood  and  scattered 
throughout  the  capillary  network  of  the  organ  into  which  they  are 
carried,  the  latter  becomes  riddled  with  tumor  nodules  (disseminated 
or  multiple  embolism).  In  dogs,  for  example,  which  are  suffer- 
ing from  cancer  of  the  thyroid  gland  the  lungs  are  as  a  rule  occu- 
pied by  great  numbers  of  nodules  of  the  same  carcinomatous  char- 
acter, the  cells  having  penetrated  from  the  cancerous  alveoli  of  the 
gland  into  the  thyroid  veins  and  having  of  course  been  carried  into 
the  lungs.  In  the  same  way  from  cancers  of  the  mammary  glands, 
the  skin,  the  nose,  etc.,  after  invasion  of  the  tributaries  of  the  vena 
cava,  metastatic  nodules  develop  in  the  lungs.  Intestinal,  gastric 
and  pancreatic  cancers  give  rise  to  metastatic  embolism  in  the  liver, 
the  tumor  cells  primarily  gaining  access  to  the  portal  vein ;  only  in 
case  they  pass  through  this  organ  does  the  lung  become  involved 
by  the  tumor  cells.  [This  is  true  in  a  general  sense  provided  the 
hsemic  route  is  followed  in  metastasis.  It  should  be  added  however 
that  these  cells  may  find  their  way  by  the  lymph  stream  through 
the  thoracic  duct  to  the  lungs,  the  liver  being  entirely  escaped.  So, 
too,  it  is  possible  by  the  minor  anastomotic  communications  be- 
tween the  portal  system  and  the  general  venous  system,  as  by  way 
of  the  veins  of  the  smaller  gastric  curvature,  lower  oesophageal 
and  azygos  veins,  that  the  cells  may  be  conveyed  to  the  lungs 
directly,  the  liver  being  evaded.] 

Malignant  bacterial  emholisui  is  determined  by  the  en- 
trance of  pathogenic  bacteria  into  the  blood  vessels,  quite  com- 
monly the  pyogenic  organisms ;  more  rarely  the  vegetable  organ- 
isms like  the  spores  of  moulds  enter  into  consideration.  Such 
germs  may  gain  entrance  into  the  circulating  blood  through  lesions 
of  the  skin  or  mucous  membranes.  Lesions  which  were  practically 
imperceptible  may  serve  as  the  point  of  entrance  [it  is  also  claimed 
by  a  number  of  persons  that  in  a  limited  degree  bacteria  may  pass, 
as  it  were  be  absorbed,  through  delicate  mucous  membranes  with- 
out the  actual  existence  of  any  structural  disturbance  of  the  mem- 
brane, as  Ravenel  has  pointed  out  in  case  of  tubercle  bacilli  passing 
through    the    normal    intestinal    wall    to    the    mesenteric    glands], 


Metastasis.  153 

the  bacteria  first  multipl_\ing-  at  this  point  of  invasion  and  then 
either  by  way  of  the  lymph  passages,  conveyed  to  the  blood. 
or  directly  growing  through  or  actively  penetrating  the  deli- 
cate walls  of  the  capillaries.  Some  bacteria  are  motile  and  are 
able  to  actively  progress  because  of  this  property,  or  because  of 
their  minute  size  ma}-  be  passively  conveyed  through  the  lymph 
spaces.  Generally  at  the  point  of  entrance  the  local  action  of  the 
bacteria  causes  a  focus  of  destruction  varying  in  type  with  the 
form  of  bacteria  present,  as  a  suppurative  liquefaction  or  ichorous 
softening  (furuncle,  suppurative  wounds  of  the  skin)  ;  coincidently 
the  destruction  of  the  walls  of  the  capillaries  and  veins  permits 
the  bacteria  to  gain  access  to  the  blood  and  circulate  with  it  and 
to  be  carried  to  the  heart  and  lung  or  from  the  intestine  to  the 
liver.  Bacteria,  too.  because  of  their  minute  size  may  traverse 
capillary  areas  and  therefore  often  pass  from  the  lesser  to  the 
general  circulation  and  become  scattered  widely  throughout  the 
system.  In  a  strict  sense  they  should  be  regarded  as  emboli,  al- 
though primarily  because  of  their  minuteness  they  occasion  no  me- 
chanical disturbances  but  remain  suspended  here  and  there  in  the 
vascular  tubes,  as  at  places  where  the  blood  current  is  temporarily 
hindered  (a  joint)  or  where  there  are  inequalities  in  the  intima 
(valves,  sharp  bends  in  the  capillaries,  renal  glomeruli).  At  such 
sites  they  induce  the  same  type  of  changes  as  at  the  point  of  en- 
trance, causing  inflammatory  reaction,  suppuration,  etc.,  and  multi- 
plving  at  first  to  the  production  of  a  definite  metastatic  focus  and 
later  making  their  mechanical  obstructive  eflfects  appreciable  when 
thev  have  developed  into  masses  and  clumps.  In  other  cases  the  bac- 
teria may  from  the  first  be  disseminated  in  the  blood  in  small  clumps. 
or  as  is  usually  the  case  they  may  adhere  to  bits  of  thrombi  which 
have  been  broken  loose.  Under  such  circumstances  mechanical 
occlusion  and  specific  action  are  to  be  expected  coincidently  or  in 
close  succession.  Precisely  as  in  case  of  simple  embolism  a  smaller 
or  larger  infarction  is  produced  and  within  the  tissue  of  the 
infarct,  filled  up  with  coagulated  blood  and  necrosed,  the  bacteria 
mav  multiply  to  great  numbers,  transforming  the  infarct,  accord- 
ing to  the  specific  properties  of  the  bacteria  of  the  embolus,  into  a 
suppurating  focus  or  breaking  it  down  into  an  ichorous  mass. 

The  most  common  example  of  malignant  embolism  is  met  with 
in  umbilical  phlebitis,  frequently  seen  in  newly  born  animals.  In 
case  after  section  of  the  umbilical  cord,  dirt  infected  with  bacteria 
(from  dung,   pus,   dust   from  the   straw   of  the   animal's  bed,   the 


154  DistitrbanCiS  of  Circidafion. 

coating  of  the  tongue  of  the  mother  animal  as  she  licks  her 
young)  comes  in  contact  with  the  umbilical  wound,  germs  capable 
of  causing  inflammation  may  penetrate  into  the  umbilical  vein 
(motile  bacteria).  These  microorganisms  rapidly  multiply  in  the 
clotted  blood  which  occupies  the  vein,  penetrating  it  possiblv  up  to 
the  liver  where  the  portal  and  umbilical  veins  unite.  Thence  by 
the  portal  current  particles  of  the  softened  and  infected  blood  clot 

are  swept  into  the  substance  of 
,  -"'"  -;?:t~-^.  ^        the  liver  and  give  rise  there  to 

multiple  abscess  formation.    Iso- 
lated  bacteria   or   small    clumps 
of    the    germs    are    carried    on- 
:^*.  ward    trom    the    liver    through 

f.'  *>pv  the    hepatic   venules    (in    calves 

perhaps  directly  by  way  of  the 
ductus     Arantii)     entering     the 
heart  and  lungs  with  the  blood 
;    '  ■■        of  the  vena  cava,  with  produc- 

tion  of  further  suppurative  me- 

Malig-nant   hsemorrhagic   infarct  of  the       tastases   Ul  the  latter.     They  may 

uie^cemre.   ''°''^-   ^"PP^''"^""'   *'^     moreover    gain    access    to    the 

general  circulation  (pulmonary 
veins,  left  heart,  aorta),  as  the  result  of  which  extensive  pyogenic 
foci  of  inflammation  of  h?emotogenous  embolic  origin  are  produced 
widely  through  the  body,  as  in  the  kidneys,  joints,  eyes  or  brain. 
Another  striking  example  of  embolic  metastasis  is  seen  in  case  of 
tuberculosis,  where  the  tubercle  bacilli  may  be  disseminated  as 
above   (cf.  chapter  on  tuberculosis). 

lymphatic  Thrombosis  and  Lymphogenous  Embolism.  The  lymph 
flowing  through  the  lymph  vessels,  the  onward  movement  of  which 
depends  partly  upon  the  pressure  with  which  the  fluid  transudes 
through  the  capillaries,  partly  upon  the  compression  upon  the 
canals  (just  as  a  sponge  is  squeezed)  by  the  movements  and  con- 
tractions of  the  organs,  is  also  subject  to  coagulation.  For  the 
most  part  lymph  coagulation  is  caused  by  the  enzymes  of  in- 
fectious toxine-producing  organisms  and  b\-  lesions  of  the  Ivmph- 
vessels  witli  adhesion  of  necrosing  leucocytes  and  separatioli  of 
fibrin  in  the  spaces.  The  lymph  canals  filled  with  lymph  coagula 
are  to  be  seen  as  broad  strands  occupied  by  the  coagulated  ma- 
terial, transparent  and  jelly-like,  as  in  the  interstices  of  the  lung 
in   croupous  pneumonia,   and   strikingly    shown,   too,   in   cutaneous 


Lxiiiplialic   Thrombosis  and   Embolism.  155 

lymphangitis.  Because  of  the  rich  and  intricate  anastomosis  of 
the  lymphatics  the  esca|)e  of  an\-  excess  of  lymph  is  easy  by  the 
collateral  paths,  and  nsually  the  obstruction  is  in  time  removed 
by  a  fatty  degeneration  of  the  clot.  Commonly  the  lymph  stasis 
therefore,  is  but  a  transient  feature.  Extensive  lymph  thrombosis 
may  hov^ever  lead  to  a  necrosis  of  the  part  involved,  from  failure 
of  removal  of  its  metabolic  products  and  the  stagnation  of  the 
lymph.  Fragments  of  the  thrombi  loosened  and  carried  away 
give  rise  to  little  of  pathological  importance,  because  of  the  rich 
collateral  communication  and  the  fact  that  the  paths  lead  into  the 
lymphatic  glands,  as  well  as  because  of  the  fine  or  molecular  dis- 
integration of  the  coagulated  material.  Only  in  case  of  the 
lymphatics  of  the  mammary  gland  is  there  to  be  apprehended  a 
direct  passage  of  such  material  into  the  blood  with  consequent 
pulmonary  embolism. 

The  lymph  channels  are  important  routes  of  transportation  of 
specific  types  of  emboli,  as  tumor  cells  and  bacteria  as  well  as  for 
the  convection  of  all  sorts  of  material  arising  from  the  disintegra- 
tion of  tissues,  dust  particles,  pigment,  and  any  other  minute  solid 
elements.  Such  substances  are  carried  along,  in  part  free  in  the 
lymphplasm  with  its  slow  current,  partly  in  the  motile  wandering 
Ivmph  corpuscles  which  load  themselves  with  small  particles;  the 
pathological  significance  of  their  convection  varxing  with  the  char- 
acter of  these  bodies.  Thus  by  the  removal  of  cUsintegrated  ma- 
terial, cellular  fragments  or  dead  bacteria,  a  tissue  or  organ  may 
be  restored  to  its  proper  functional  capacity,  a  sort  of  street-clean- 
ing being  accomplished ;  but  on  the  other  hand  the  convection  of 
toxic  matter,  of  cells  or  microbes  capable  of  multiplication,  serves 
to  establish  more  local  points  (or  generalization)  of  the  disease.  A 
few  examples  may  render  this  more  clear.  In  case  of  hremorrhagic 
extravasations,  as  after  the  fracture  of  a  bone,  the  entire  hsemor- 
rhagic  focus  gradually  disappears,  the  disintegrating  blood  corpus- 
cles being  taken  up  by  the  lymph  corpuscles  wandering  about  and 
carried  to  the  lymph  glands  for  further  destruction  (as  a  result 
of  which  the  lymph  glands  in  the  neighborhood  of  such  hsemor- 
rhagic  areas  become  the  seat  of  a  rusty  brown  discoloration). 
Carbonaceous  particles  inhaled  and  lodged  in  the  lung  are  carried 
along  the  lymph  passages  to  the  bronchial  lymph  nodes,  coloring 
them  black.  Virulent  streptococci  wdiich  have  gained  entrance  to 
the  mouth  and  pharynx  are  taken  up  by  leucocytes  wandering  out 
and    in   the    mucous    lining,    carried    primarily   to   the    pharyngeal 


156  Disturbances  of  the  Blood. 

lymphglands,  where  they  may  perhaps  multiply  and  give  rise  to 
suppuration ;  thence  they  may  travel  from  one  lymph  node  to 
another  (retropharyngeal,  cervical,  thoracic),  in  each  setting  up 
new  foci  of  suppuration,  until  they  finally  reach  the  blood  and  pro- 
duce pyaemia. 

No  matter  how  minute  the  lesion  of  the  skin  or  mucous  mem- 
brane, infectious  bacteria  may  from  some  source  gain  access  to 
the  lymphatic  radicles  and  occasion  their  specific  processes  in  the 
lymph  channels  and  at  their  points  of  deposit  in  the  lymph  glands 
(cf.  tuberculosis  and  carcinoma).  Lymphogenous  extension  or 
embolism  is  therefore  to  be  regarded  as  an  important  factor  in  the 
generalization  of  local  infectious  processes. 

Pathological  Changes  of  the  Blood. 

The  blood  supplies  the  tissues  with  the  oxygen  essential  to  their 
life,  besides  the  albuminates,  carbohydrates  and  water ;  it  removes 
their  metabolic  products  and  is  the  principal  factor  in  the  distribu- 
tion of  heat;  it,  therefore,  maintains  the  functions  of  the  nervous 
system,  the  heart  and  all  of  the  organs  as  their  liquid  nutrient,  their 
source  of  heat  and  their  cleansing  fluid.  In  its  manifold  relations 
to  the  tissues,  in  its  function  of  giving  and  receiving  on  so  many 
sides,  there  arises  constant  change  in  the  quantity  and  composition 
of  the  blood,  limited,  of  course,  within  certain  bounds  and  relations 
set  by  the  tissue  requirements.  When  blood  is  lost,  fluid  is  taken 
into  the  vessels  from  the  tissues  and  corpuscles  are  supplied  by  the 
blood  forming  organs  to  the  eventual  restoration  of  the  blood. 
When  an  excessive  amount  of  water  is  absorbed  there  follows  rapid 
excretion  of  the  superfluous  quantity  through  the  kidneys ;  and  in 
analogous  fashion  the  variations  in  its  chemical  constitution  are 
continually  undergoing  adjustment.  \\'e  have  yet  to  discover 
wherein  lies  the  exact  and  delicate  regulation  of  the  quantity  and 
quality  of  this  complex  liquid ;  at  all  events  the  changes  -in 
chemical  composition  involve  continually  repeated  stimulation  of 
the  nerves  of  the  blood  vessel  walls,  of  the  cells  of  the  hgemopoietic 
organs  and  all  secretory  cells  upon  which  the  hremic  composition 
depends.  As  soon  as  this  regulation  is  disturbed  the  variations 
in  the  volume  and  proportionate  composition  of  the  blood  deviate 
from  the  physiological  limits,  and  hcxmic  anomalies*  are  said  to 
exist. 

*The  word  ili/scrasia  was  formerly  employed  in  this  connection,  but  was  wittiout 
exact  significance,  being  applied  by  some  to  any  blood  abnormality,  by  others  to  long 
persisting  faults  in  the  proportionate  presence  of  its  constituents  or  simply  to 
impurities  of  the  blood  from  the  presence  of  special  substances.  The  word  may  be 
dispensed  with. 


Plethora  and  Oligcumia.  157 

It  can  readily  be  appreciated  why  there  are  so  many  types  and 
degrees  of  blood  abnormalities  when  it  is  recalled  that  of  neces- 
sity pathological  changes  in  the  blood  must  follow  any  alteration 
in  the  efficiency  of  the  organs,  the  metabolic  processes  of  which  arc 
constantly  removing  from  or  adding  to  the  blood  so  many  elements. 

The  amount  of  blood  obtainable  from  the  domestic  animals  at 
slaughter  is  subject  to  such  wide  variation,  as  Bollinger  and  Berg- 
man have  pointed  out,  that  it  is  clear  'that  we  can  have  no  safe 
basis  for  determining  the  existence  of  an  excessive  volume,  of  a 
condition  which  may  be  termed  full  bloodedness  or  plethora,  in  any 
subject,  either  from  the  quantity  obtained  at  slaughter  or  deduced 
from  symptoms.     The  healthy  animal  very  quickly  gets  rid  of  ex- 
cesses   introduced    experimentally    into    the    body,    whether    it    be 
blood  of  the  identical  species,  blood  serum  or  indifferent  fluids ;  and 
the  transient  plethora  caused  by  transfusion  causes  no  disturbances 
worth  mentioning.     The  blood  vessels  are  in  fact  never  filled  to 
their    full   capacity    collectively ;   the   vast    multitude   of   capillaries 
capable  of  further  dilatation  can  accommodate  a  large  volume  of 
fluid  in  excess  of  their  ordinary  content.     Experiment  upon  ani- 
mals  shows  that   in   dogs   the  blood   volume   may  be  doubled  by 
transfusion,  a  quantity  representing  eight  to  twelve  per  cent,  of  the 
body  weight  introduced,  without  injury  to  the  animals;  danger  to 
life  occurs  only  after  the  introduction  of  a  still  greater  amount 
(Samuel).     The  excess  of  fluid  transudes  from  the  vessels  and  is 
eliminated   from  the  body  in  the  course  of  a   few  days  with  the 
urine;  the  superfluous  blood  cells  are  destroyed  in  the  liver  and 
other  organs.     Whether  a  plethora  of  actual  pathological  signifi- 
cance ever  occurs  in  animals  is  quite  unknown. 

Diminution  of  the  volume  of  the  blood,  known  as  blood 
impoverishment,  oligaemia  or  general  anaemia,  has  associated 
with  it  a  decrease  of  the  number  of  blood  corpuscles,  known 
technically  as  oligocythcEmia;  usually,  too,  the  converse  is  true. 
From  a  practical  standpoint  it  is  difficult  to  draw  any  fine  distinc- 
tions as  to  whether  the  blood  is  normal  as  far  as  the  volume  of  its 
fluid  is  concerned  and  only  the  cellular  elements  deficient,  or 
whether  the  plasma,  its  salts  and  other  constituents  have  under- 
gone the  greater  reduction ;  for  which  we  are  accustomed  to  regard 
the  loss  and  destruction  of  the  erythrocytes,  the  most  conspicuous 
of  the  blood  constituents,  as  the  principal  pathological  feature.  In- 
asmuch, however,  as  there  is  a  close  interrelation  of  these  altera- 
tions, the  one  dependent  upon  the  other,  there  are  apt  to  exist  many 


158  Disturbances  of  the  Blood. 

peculiar  phenomena  in  these  instances,  which  have  thus  far  been 
imperfectly  studied ;  for  example,  the  red  blood  corpuscles  may 
undergo  reduction  and  disintegration  because  the  plasma  contains 
some  unusual  saline  or  an  excess  of  water  or  because  some  spe- 
cific hgemolytic  substance  has  become  mingled  with  it.  Briefly 
speaking,  it  is  customary  to  speak  of  general  anaemia  in  a  subject 
whose  mucous  membranes  and  skin  persistently  appear  very  pale, 
whose  muscular  tissue  and  viscera  have  at  autopsy  the  pallor  char- 
acteristic of  a  slaughtered  animal  and  in  which  in  life  there  ex- 
isted a  condition  of  general  weakness.  The  contrast  between 
the  peculiar  tint  of  the  organs  and  the  deep  red  color  given  by  the 
full  capillary  blood  serves  better  to  indicate  the  reduction  in  the 
volume  of  the  blood  than  the  amount  which  can  be  obtained  in 
the  heart  and  large  vessels  and  which  can  be  estimated  only  with 
extreme  difficulty.  Oligocythsemia  is  determined  for  a  cubic  milli- 
meter of  blood  by  microscopic  counts  of  the  cells  with  special 
measuring  apparatus;  diminution  of  the  hsemoglobin  content  can 
be  determined  only  by  chemical  methods.  [Clinically  this  latter 
is  estimated  by  comparison  of  either  the  whole  or  the  diluted  blood 
with  standard  color  scales,  each  graduation  of  tint  representing 
a  certain  proportion  of  hsemoglobin.  Matching  of  colors  always 
involves  a  large  personal  equation  and  at  best  can  only  be  approxi- 
mate, even  were  it  established  that  the  supposedly  standard  refer- 
ence scale  were  entirely  correct — which  is  not  the  case.  How- 
ever, as  an  approximation  only  and  as  a  fairly  ready  means  of 
comparison,  these  color  tests  have  at  least  a  clinical  value.] 
The  least  complicated  form  of  oligjemia  is  that  occasioned  by 
blood  loss  from  injury  to  the  vascular  apparatus,  hcemorrhagic 
anccmia,  following  wounds  and  lacerations  of  the  vessels,  venesec- 
tion or  the  removal  of  blood  by  blood  sucking  parasites.  A  blood 
loss  exceeding  three  per  cent,  may  be  dangerous  to  life  (external 
or  internal  injuries)  and  sudden  haemorrhages  of  still  smaller  vol- 
ume from  the  large  vessels  may  be  fatal.  [While  exceptionally 
this  statement  may  be  true  where  there  are  other  factors  as  nerv- 
ous shock  involved,  the  limits  of  non-fatal  blood  loss  as  here  given 
are  for  ordinary  cases  quite  too  low.  As  much  as  one-third  the 
volume  of  blood  has  often  been  withdrawn  without  fatal  collapse.] 
The  volume  of  fluid  lost  by  non-fatal  hgemorrhage  is  soon 
restored  by  absorption  of  water  from  the  tissues  and  ingesta ;  while 
the  corpuscles  and  albuminous  material  are  reformed  in  the  course 
oi   a    few    weeks    or    months.     In    fatal    haemorrhage    there    occur 


Chaii^i^cs  in   the  Erythrocytes  in   Anccniias.  159 

phenomena  of  suffocation,  lowering  of  blood  pressure  and  uncon- 
sciousness (ansemia  of  the  brain).  After  haiimorrhage  proteid 
/netabolism  is  increased;  metabohsm  of  fats  is.  however,  decreased 
because  of  the  diminished  power  of  combustion.  Hence  repeated 
venesections  are  appropriate  treatment  where  it  is  desired  to  in- 
crease the  deposition  of  fat  and  tlic\-  are  employed  as  aids  to  fat- 
tening animals. 

General  anaemia  may  also  be  brought  about  by  insufficient  nutri- 
tion or  improper  assimilation  of  food,  as  well  as  by  diseases  and 
injuries  of  those  tissues  which  supply  definite  blood  constituents. 
Here  are  particularly  included  various  affections  of  the  stomach  and 
intestine,  hepatic  diseases  and  alterations  of  the  lymphatic  tissues ; 
but  in  arldition  to  such  disturbances  there  is  a  wide  further  possi- 
bility of  the  establishment  of  an  ansemia  from  disease  of  the  many 
other  tissues  which  contribute  to  blood  formation.     A  number  of 
agencies  are  known  to  be  capable  of  inducing  the  condition  by  caus- 
ing the  destruction  of  the  blood  corpuscles,  perhaps  to  such  a  de- 
gree that  regenerative  effort  can  no  longer  efficiently  restore  the 
loss,  as  certain  parasites  of  the  blood  (trypanosomes)  and  poison- 
ous or  toxic  products  of  metabolism. 

Among    the    most    notable    symptoms    of    man\-    anremias    are 
changes  in  the  form  and  structure  of  the  erythrocytes.     In  place 
of  the  circular  discs  there  may  be  met  irregular  pyriform,  club- 
shaped    or    indented  elements    of    various    size,    cells    containing 
vacuoles    (cavities,   hollow   spaces),   and   nucleated   red  corpuscles. 
A  blood  preparation  showing  such  multiform  cells  of  varying  ap- 
pearances is  said  to  exhibit  poikilocytosis    (  ttoikIXos,  variable,   con- 
fused,   involved).      Recently   alterations    in   the   staining   reactions 
of  the  corpuscles  have  been  made  out.     The  normal  cells  invariably 
take    up    only    one    tint    from   certain    staining   combinations;    the 
stroma    of   young   forms,    degenerating   and    dead   cells,    however, 
may  assume  several  colors    (polychromatophUia).     The  occurence 
of  nucleated  red  corpuscles  in  the  circulating  blood  is  an  evidence 
of  active  regeneration  of  these  elements,  and  is  often  encountered 
in  the  anaemias.     Especially  large  cells  of  this  type  are  sometimes 
met    {megalohlasts,    gigantobhtsts),    a    peculiarity    interpreted    as 
evidence    that    regeneration    is   taking    place    with    extreme    haste, 
such  cells,  otherwise  only  seen  in  the  bone  marrow  as  early  stages 
of  the  erythrocytes,  entering  the  circulation  in  these  cases  as  im- 
mature   elements    (Krehl).     The   increased   cellular   muhiplication 
in  the  bone  marrow,  the  principal  site  of  the  formation  of  erythro- 


i6o  Disturbances  of  the  Blood. 

cytes,  causes  in  ansemias  large  areas  of  this  tissue  to  return  to  the 
condition  of  red  marrow  (normally  only  young  growing  animals 
have  much  red  marrow ;  in  adults  medullary  blood  formation  is 
limited  to  a  few  bones  according  to  the  amount  of  blood  required 
to  be  formed ;  change  of  the  marrow  to  the  red  state  and  pro- 
duction of  this  condition  in  many  of  the  bones  may  be  brought 
about  in  animals  by  venesection — Naunyn,  Litten  and  Orth). 

In  severe  forms  of  ansemia  not  occasioned  by  actual  blood  loss  the  pro- 
portion of  iron  in  the  liver,  spleen  and  kidneys  becomes  abnormally  high,  this 
feature  invariably  indicating  exaggerated  destruction  of  the  red  cells. 

From  a  variety  of  causes,  particularly  the  influence  of  certain 
poisons  (salts  of  the  biliary  acids,  snake  venom,  bacterial  toxines) 
and,  too,  the  transfusion  of  heterogeneous  blood  (blood  from  a 
different  species  of  animal),  the  h?emoglobin  may  undergo  solution 
and  separation  from  the  erythrocytes  into  the  plasma  {hccnio- 
globincemia) .  The  coloring  matter  thus  freed  gives  the  plasma 
or  serum  a  difl^use  wine-red  color.  A  portion  of  the  haemoglobin 
is  taken  up  by  the  liver  and  transformed  into  biliary  pigment,  and 
the  remnants  of  the  injured  and  therefore  disintegrating  blood 
corpuscles  are  to  be  found  in  the  liver  and  in  the  spleen  (also  in 
the  marrow),  these  organs  sometimes  becoming  considerably  swol- 
len and  excessive  bile  formation  taking  place.  The  bulk  of  the 
liberated  haemoglobin  is  removed  by  the  kidneys,  causing  more  or 
less  harm  to  these  organs  and  giving  to  the  urine  a  blood  red  to 
black  discoloration  (hcemoglobincemia) .  These  changes  are  ob- 
served not  only  in  association  with  severe  infections  and  intoxica- 
tions in  cattle,  but  are  also  seen  after  muscular  strain  and  chilling, 
especially  in  horses  and,  too,  in  human  beings  (infectious,  toxic, 
paroxysmal,  myogenous,  rheumatic  hsemoglobinuria).  Some  of 
the  haemoglobin  in  hjemoglobinaemia  which  remains  in  the  blood  is 
converted  into  methasmoglobin ;  this  change  may  also  affect  the 
coloring  matter  within  the  corpuscles,  and  is  apt  to  result  par- 
ticularly from  the  action  of  certain  poisons  (antipyrin,  potassium 
chlorate).  It  gives  rise  to  an  appreciable  sepia-brown  coloration 
of  the  blood  (niethcemoglobincemia) .  There  always  coexist  with 
this  group  of  blood  changes  serious  diseases  of  the  subject ;  the 
haemoglobin,  freed  from  the  cells  and  altered  in  its  constitution, 
useless  for  respiratory  purposes,  is  no  longer  capable  of  taking  up 
and  giving  off  oxygen  (Krehl),  and  the  disintegrating  blood  cells 
give   origin  to  substances   which  may  cause  coagulation  to  take 


The  Leucocytes  in   Aiucinias.  i6i 

place   here   and   there    in    the    vessels,   occlusion    of   the   capillaries 
and  serious  lesions  of  the  renal  epithelial  cells. 

Oligsemia  is  occasionally  associated  with  a  truly  watery  condition  of 
the  blood,  as  where  in  case  of  haemorrhage,  blood  imiioverishment,  inani- 
tion, or  renal  disease  the  blood  becomes  deficient  in  albumen,  the  vessels 
become  filled  with  the  fluid  from  the  tissues  in  an  effort  to  restore  the 
deficiency;  such  a  condition  is  termed  hydrccntia  (oligccniia  serosa).  So. 
too,  the  increase  in  the  proportion  of  water  with  increase  of  the  total 
volume  of  blood  (plethora  aquosa.  serosa)  may  lie  thought  of  as  a 
pathological  possibility;  however,  proper  information  is  as  yet  lacking 
concerning  these  pathological  conditions  and  the  relation  between  quanti- 
tative changes  of  the  serum  albumen  to  the  proportion  of  water  in  the 
blood.  Normally,  large  excesses  of  water  known  to  be  rapidly  absorbed 
from  the  stomach  and  intestine  into  the  blood  are  quickly  passed  off 
through    the    kidneys. 

Of  the  pathological  conditions  of  the  leucocytes  or  white  blood 
cells  and  their  reduction  or  increase  in  numbers  in  the  circulating 
blood  our  knowledge  is  only  of  the  most  superficial  character. 
To  what  extent  the  morphological  and  tinctorial  peculiarities  of  the 
individual  forms  and  groups  of  leucocytes  and  lymphocytes  nor- 
mally found  in  the  blood  are  characteristic  of  the  origin  and  of  the 
role  of  these  cells  is  a  matter  requiring  further  investigation. 
These  cells  are  of  especial  interest  to  the  pathologist  from  the  fact 
that  they  are  either  attracted  or  repelled  by  chemical  materials  in 
the  tissues  and  by  various  particulate  elements  which  may  give 
origin  to  the  former  (positive  and  negative  cheinotaxis).  Be- 
cause of  the  power  possessed  by  these  cells  of  approaching  or 
receding  from  a  given  point  like  motile  organisms,  of  taking  into 
their  substance  small  bodies  which  they  encounter — an  act  which 
is  to  be  regarded  as  an  attempt  to  obtain  nourishment  (cellular 
devouring  capacity,  pliogoeytosis) — they  may  be  thought  of  as 
playing  the  part  of  "scavengers  of  the  organism"'  (products  of 
disintegration,  dust  particles,  dead  cells  and  tissues,  dead  bacteria, 
etc.,  all  being  removed  in  this  manner).  They  may  however  by 
identically  the  same  mode  of  action  come  to  serve  as  carriers  of 
infection  in  case  a  living  bacterium  or  animal  microorganism  hap- 
pen to  be  taken  up  by  them.  A  microorganism  not  necessarily 
destroyed  in  the  substance  of  the  leucocyte,  but  possibly  actually 
multiplying  there,  may  be  carried  away  to  a  new  situation  and 
there  renew  its  toxic  influences,  especiall\"  if  the  phagocytic  cell  be 
destroyed  by  its  poison.  [.Metschnikofif  urges  strongly  that  after 
appropriation   of  a   microbe  by   a   phagocyte,   the    former   may   be 


i62  Disturbances  of  the  Blood. 

regarded  as  entirely  destroyed  or  as  seriously  impaired  in  its 
vitality.]  It  is  readily  observed  in  suppurations  undergoing 
metastasis  (cf.  metastasis),  in  swine  erysipelas  and  other  bac- 
terisemias,  that  many  of  the  leucocytes  are  loaded  with  the  specific 
germs. 

Negative  chemotaxis,  too,  the  movement  of  the  leucocytes  away 
from  certain  poisons  or  more  frequently  the  mere  failure  of  attrac- 
tion of  the  cell  toward  these  substances,  is  capable  of  explaining  a 
number  of  points  connected  with  disease  and  immunity.  For  ex- 
ample, as  shown  by  the  extremely  interesting  studies  of  Besson, 
Leclainche-Vallee,  Vaillard  and  A^incent,  non-virulent  but  living 
germs  (spores)  of  tetanus,  malignant  oedema  and  blackleg  are 
englobed  by  leucocytes  and  ingested  and  thus  prevented  from  de- 
velopment and  from  becoming  virulent ;  virulent  germs  of  these 
same  sorts,  however,  prevent  the  leucocytes  from  entering  the  tis- 
sues because  of  the  toxines  to  which  they  give  origin  and  are 
therefore  not  taken  up  by  the  phagocytes,  but  continue  their  harm- 
ful action  upon  the  tissues  in   which  they  exist. 

The  general  group  of  leucocytes  in  the  blood  is  subject  to  con- 
siderable variation  in  number,  even  under  normal  conditions. 
After  taking  food  or  violent  muscular  exercise  there  may  be 
uniformly  observed  an  increase  in  their  number  ( physiological 
leucocytosis  or  hypcrlcucocytosis) ,  apparently  occasioned  by  the 
attractive  influence  exerted  by  various  proteid  matters,  fatigue 
stuffs,  etc.,  which  have  entered  the  blood.  In  inflammations,  sup- 
purations, and  infectious  fevers  a  similar  increase  in  the  number 
of V  leucocytes  distributed  throughout  the  blood  occurs  {pathological 
hyperleucocytosis) ,  similarly  ascribable,  so  far  as  indicated  by  ex- 
periment, to  chemical  attraction  and  the  circulation  in  the  blood 
of  substances  stimulating  the  leucocyte-forming  tissues  to  greater 
production.  (Injection  of  bacterial  proteins  and  other  proteids  into 
the  blood  is  particularly  likely  to  be  followed  by  hyperleucocytosis). 
[While  there  are  a  few  exceptions  to  the  usual  occurrence  of 
leucocytosis  in  acute  infections,  it  is  in  a  general  way  to  be  in- 
terpreted as  an  unfavorable  feature  when  such  increase  fails  to 
take  place  (leucopenia)  ;  either  the  subject  being  in  such  deterio- 
rated state  that  the  usual  reaction  is  impossible  and  the  resistance 
to  the  disease  much  below  par,  or  the  smallness  of  number  of  these 
protective  cells  itself  determining  the  failure  of  sufficient  antago- 
nism. Cases  marked  by  such  unusual  leucopenia,  with  the  excep- 
tion as  above  suggested  of  a  few  special  forms  of  disease,  are  apt 
to  terminate  fatally. 


f  I' 


The  Leucocytes  in   Anccmias.  163 

To  a  certain  extent  the  increase  of  this  or  that  particular  form 
of  leucocyte  is  of  diag-nostic   importance.     In  brief   we   reco.^nize 
as  the  most  common  form  of  white  blood  corpuscle  the  i)olymor- 
phonuclear  neutrophile  cells  (containing  multiple  nuclei  or  a  single 
polymorphous  nucleus,  and  having  numerous  fine  granules  in  the 
cytoplasm  wdiich  elect  a  combination  of  the  acid  and  alkaline  dyes 
in  staining  with  such  mixtures,  becoming  purplish  with  methylene 
blue    and    eosin    for    example).     An    increase    of    these    elements, 
spoken  of  simply  as  leucocyfosis  or  hyperleucocytosis  according  to 
its  grade,  is  commonly  m.et  in  a  number  of  infections,  particularly 
those    of    the    septic    group.     There    are    normally   present   in   the 
blood    a    few    similar    leucocytes     which    have,    however,    in    their 
cytoplasm  rather  coarse  granules  which,   from  an   acid  and  basic 
combination    of    dyes,    select    the    former,    being    therefore    called 
oxvphile  cells    (or  because  eosin  is  the  acid  part  of  the  common 
methylene  blue  and  eosin  solutions  and  their  cell  granules  appro- 
priate the  red  of  the  eosin.  these  cells  are  often  called  eosinophile 
cells).     These  oxyphile  cells  may  become  increased  in   a  number 
'of  conditions,  but  this  increase,  know^n  as  eosiiiophilia,  is  especially 
notable  in  the  blood  of  animals  or  human  beings  subject  to  some 
of  the  animal  parasites   as  the  trichina   or  hookworm.     Tn    pseu- 
doleukremia   and   lymphatic   leukaemia   the  lymphocytes,    cells  with 
single  large,  deeply  basic  staining  nuclei  and  with  fine  basophilic 
granules  in  the  scanty  cytoplasm,  are  especially  increased.     Tn  the 
common  lieno-medullary  leukaemia   there   is   special   increase   in   a 
large   type   of    leucocyte    not   normally   present    in   the   blood   but 
natural   to   the  bone-marrow",   known   as   a   myelocyte,   with   large 
nucleus  taking  the  basic  stain  faintly   and   with  fine   neutrophilic 
granules  in  the  cytoplasm.] 

Where  there  is  such  an  increase  of  leucocytes  in  the  blood  that 
thev  equal  or  exceed  the  number  of  erythrocytes  in  the  drop  from 
which  the  cell  count  is  made,  or  if  certain  cells  normally  present 
in  but  meager  numbers  are  unusually  numerous  [the  mononuclear 
cells  above  noted  as  myelocytes]  the  name  leiikcvmia  is  employed 
to  denote  the  condition.  [The  actual  number  has  been  known 
to  equal  that  of  the  erythrocytes,  but  this  is  exceptional ;  and  the 
present  conception  of  leukaemia  concerns  rather  the  type  of  cell 
present  in  the  blood,  the  myelocyte,  than  the  actual  numbers  at- 
tained.] In  this  disease  the  blood  is  apt  to  be  changed  in  its 
macroscopic  appearance  as  well,  becoming  of  a  light  red  or  rasp- 
berry color.     There  also  occur  hyperplastic  changes  in  the  various 


164  Disturbances  of  the  Blood. 

lymphoid  structures  of  the  body  (lymph  glands  [in  lymphatic 
leukaemia]  ;  bone-marrow  and  spleen  [in  lieno-medullary  leu- 
kaemia] )  ;  and  the  coincidence  of  a  general  debility,  fever,  and 
tendency  to  hemorrhage  mark  the  condition  as  a  serious  affection. 
Nothing  definite  is  known  of  the  aetiology  of  the  affection  either 
in  man  or  the  animals;  it  has  been  conjectured,  however,  that  the 
cause  may  be  of  an  infectious  nature. 


DISTURBANCES  OF  M-ETABOLISM;  RETRO- 
GRESSIVE AND  NECROTIC  PROCESSES 

Faults  of  Heat  Regulation;  Hyperthermia;  Fever. 

The  temperature  peculiar  to  the  various  warni-blooded  animals 
is  constantly  maintained  in  health  at  the  same  level  within  narrow- 
limitation  by  the  delicate  and  accurate  regulatory  mechanism  of 
the  body.  With  every  change  in  the  surrounding  temperature  and 
other  external  influences  there  occurs  special  adaptation  of  heat 
production  and  heat  dissipation  on  the  part  of  the  animal  body.  If 
an  excess  of  heat  be  produced  within  the  body  from  exaggeration 
of  metabolism  (muscular  activity,  ingestion  of  large  amounts  of 
food),  excessive  heat  dissipation  follows;  the  cutaneous  blood  ves- 
sels dilate  and  the  system  loses  in  consequence  a  greater  amount 
of  heat  from  its  surface  by  conduction,  by  radiation  and  if  need  be 
by  perspiration,  as  well  as  by  free  evaporation  of  moisture  in  the 
lungs.  In  case  the  body  suffers  unusual  heat  loss  (cold  environ- 
ment) heat  dissipation  is  diminished  by  constriction  of  the  cutaneous 
vessels,  and  the  chemical  activities  in  the  tissues  increase  heat  pro- 
duction by  accelerating  decomposition,  that  is.  the  combustion  of 
carbohydrates  and  fats,  particularly  in  the  musculature.  Rich 
food  suppl}-  and  bodil\-  activity  increase  the  production  of  heat ; 
and  by  these  means  and  by  simple  diminution  of  heat  dissipation 
the  warm  blooded  animal  is  enabled  to  maintain  its  proper  tem- 
perature in  spite  of  marked  chilling. 

The  human  being  in  state  of  health,  possessing  additional  means 
of  conserving  his  warmth  by  a  number  of  layers  of  warmed  air 
(clothes)  about  his  body,  maintains  an  average  body  temperature 
of  37.2° — 37.4°  C.,  the  variation  from  morning  to  evening  being 
about  one  or  one  and  one-half  degrees.  The  horse,  according  to 
Friedberger-Frohner,  has  a  normal  temperature  of  37.5° — 38.5°  C; 
the  cow,   38° — 39°    C. ;  the  sheep  and   goat,   39° — 40.5°   C. ;  hog, 


i66  Teuipcrafurc  Disturbances. 

38°— 40°    C;    dog,    37-5"— 39°    C.;    cat,    38°— 39°     C. ;    birds, 
4i.5°-42.5°  C. 

The  warm  blooded  animal  maintains  the  constant  physiological 
level  of  temperature  by  the  continued  operation  of  the  heat  dis- 
sipating powers ;  if  there  were  no  such  loss,  the  amount  of  heat 
production  would  be  sufficient  to  cause  an  increment  of  about  one 
degree  centigrade  in  the  temperature  of  the  blood  every  half  hour. 

Passive  Hyperthermia.  By  limitation  of  heat  dissipation 
the  body  may  become  overheated,  particularly  when  the  cause 
is  some  external  physical  influence  which  hinders  heat  loss  by 
evaporation.  Although  in  a  dry  atmosphere  where  there  is  no 
restriction  to  evaporation  the  body  is  capable  of  enduring  even  high 
temperatures  of  the  surrounding  air,  the  body  heat  increases  rap- 
idly in  a  hot,  moist  atmosphere,  heat  loss  by  evaporation  being 
impossible,  and  all  the  more  if  in  addition  there  be  increased  pro- 
duction from  muscular  exercise.  In  a  warm  bath  of  40° — 41°  C. 
the  human  body  temperature  may  even  in  half  an  hour  reach  40°  C. ; 
in  water  of  37°  C,  it  rises  about  1°  C.  in  an  hour,  and  in  an  hour 
and  a  half  about  2°  C. 

Animals  closely  packed  in  hot  railway  cars  experience  consid- 
erable increase  of  temperature ;  in  warm,  damp  air  animals  closely 
herded  in  long  drives  (droves  of  hogs,  oxen  yoked  to  wagons)  may 
have  their  temperature  reach  more  than  40° C.  Under  such  cir- 
cumstances where  only  external  physical  conditions  render  the 
regulation  of  the  body  temperature  impossible  or  where  (perhaps 
coincidently)  unusual  accession  of  heat  production  occurs  because 
of  exceptional  muscular  exercise,  there  is  really  no  true  febrile  tem- 
perature present,  but  rather  only  a  passive  heat  accumulation, 
passive  hyperthermia;  the  mechanism  of  heat  dissipation  is  acting 
in  its  fullest  capacity  and  is  insufficient  only  because  the  demands 
upon  it  are  excessive  (Krehl).  Thermolysis  so  far  as  the  animal 
body  is  concerned  is  not  at  fault ;  but  fails  because  of  conditions 
existing  in  the  external  surroundings. 

Whether  pathological  results  follow  such  passive  hyperthermia 
will  depend  upon  the  persistence  of  the  condition  and  the  subject's 
power  of  adaptation.  Men  and  animals  living  in  tropical  coun- 
tries give  evidence  upon  this  last  point ;  and,  too,  it  is  commonly 
seen  that  when  a  number  of  individuals  are  subjected  to  excessive 
temperatures  there  are  only  certain  ones  who  suffer  pathologically, 
those  probably  whose  thermo-regulatory  mechanism  is  of  inferior 
efficiency.     Passive  hyperthermia  may  reach  42° — 45°  C,  and  may 


Fever.  167 

terminate  fatally  {heat  stroke).  The  occurrence  of  a  heat  stroke 
is  marked  by  symptoms  of  general  weakness,  dizziness,  fainting 
attacks,  and  marked  acceleration  of  the  pulse,  these  probably  being 
mainly  dependent  upon  disturbances  of  brain  and  myocardium,  al- 
though upon  this  point  there  is  need  of  further  study. 

Fever  {fehris,  from  fervere,  to  be  hot)  is  a  state  of  the  body 
in  which  because  of  some  disturbance  of  metabolism  the  regulation 
of  the  body  temperature  to  a  mean  level  has  ceased.  The  chief 
and  most  constant  evidence  of  fever  is  the  abnormal  increase  of 
the  temperature  of  the  blood,  or  internal  body  temperature.  This 
febrile  hyperthermia  or  fever  heat  may  exceed  the  normal  tem- 
perature of  the  animal  perhaps  but  half  a  degree  or  by  from 
two  to  five  degrees  centigrade.  It  is  characterized  by  marked  re- 
sistance to  influences  causing  heat  dissipation  and  by  considerable 
variation ;  and  is  accompanied  by  increased  tissue  waste,  changes 
in  the  type  of  and  increased  frequency  of  the  arterial  pulse,  increase 
in  the  rate  of  respiration,  diminution  and  alterations  in  the  various 
secretions,  particularly  in  the  urine,  disturbances  in  the  sensory 
apparatus,  increased  thirst  and  loss  of  appetite.  This  group  of 
symptoms,  which  occur  with  the  heightened  temperature  and  with 
it  go  to  make  up  the  clinical  picture  of  fever,  are  to  a  slight 
extent  directly  dependent  upon  the  increased  temperature  of  the 
blood  (for  example,  the  number  of  cardiac  movements  and  respira- 
tions), but  for  the  greater  part  are  the  results  of  the  complex 
action  of  the  causes  of  the  fever.  The  main  point  in  the  conception 
of  fever,  with  its  febrile  excess  of  temperature,  is  that  the  latter 
is  not  the  mere  result  of  external  physical  influences  restricting 
thermolysis,  or  of  muscular  activity,  but  that  there  are  certain 
metabolic  processes  in  operation  which  are  due  to  the  presence  of 
special  temperature  producing  substances  {pyrogenetic  substances) 
which  give  origin  to  the  hyperthermia.  How  the  heat  equilib- 
rium is  aft'ected  by  such  substances,  whether  they  directly  dis- 
engage the  heat  from  the  cells  and  cellular  groups  or  whether 
they  act  indirectly  through  a  heat  centre,  is  not  as  yet  certain  and 
cannot  even  in  a  general  way  be  explained.  These  pyrogenetic 
substances  vary  much  among  themselves  and  the  reaction?  which 
they  give  rise  to  are  by  no  means  uniform.  P""ever  may  be  thovight 
of  as  an  indicator  (Wassermann)  that  some  peculiar  metabolic 
processes  are  in  operation  in  the  body  accompanied  by  tissue 
destruction  and  the  production  of  antitoxic  and  bactericidal  sub- 
stances and  precipitins ;  and  may  be  considered  as  an  associated 


i68  Temperature  Disturbances. 

or  partial  inaiii testation  of  a  complex  reaction  to  which  the  or- 
ganism is  prompted  by  the  invasion  of  substances  foreign  to  the 
system.  From  this  it  may  be  appreciated  that  the  idea  of  febrile 
temperature  and  of  fever  is  in  reality  principally  based  on  the 
aetiology  of  the  condition ;  the  existence  of  proper  causes  of  fever, 
the  presence  of  pyrogenetic  substances,  is  the  factor  determining 
whether  we  are  or  are  not  to  regard  and  speak  of  a  hyperthermia 
as  febrile. 

Microorganisms,  both  vegetable  and  animal,  constitute  a  most 
important  group  of  these   pyrogenic  substances,   acting  especially 
through  their  chemical  toxic  products.     It  is  this  fact  which  ex- 
plains why  the  course  of  nearly  all  the  acute  infections  is  accom- 
panied  by   fever.     It   can  be  promptly   induced  by   infection  with 
various  specific  germs ;  inoculation  with  anthrax  bacilli  or  pyogenic 
cocci,  with  trypanosomes  or  piroplasmata,  each  occasions  a  febrile 
reaction.     After  Charrin  and  Ruffer  pointed  out  that,  by  injecting 
into    rabbits    cultures    of    bacillus    pyocyaneus    which    had    been 
sterilized  and  freed  from  living  germs,  febrile  temperature  acces- 
sion ma}'  be  induced,   a  number  of  observers  have   demonstrated 
that  similar  effects  may  be  obtained  by  employing  the  metabolic 
products  of  a   number   of  other   bacteria.      This   means   therefore 
that  we  are  here  dealing  with  a  group  of  soluble  substances  passing 
from  the  substance  of  the  microorganisms  into  the  fluids  and  tissues 
of   the   affected   body,    either   secreted    by   the    living   bacteria    or 
representing  some  of  the  results  of  disintegration  of  the  bacterial 
body    (toxines,  proteins,  alkaloids  and  a  variety  of  substances  of 
different  composition).     According  to  E.  Centanni,  practically  the 
entire  group  of  bacteria  produce  a  practically  uniform  fever  toxine 
which  he  isolated  from  cultures  and  named  pyrotoxina  bacteritica, 
and  with  which  he  was  able  to  reproduce  in  rabbits  all  the  main 
clinical  features  of  the  infectious  fevers. 

This  thermotoxine  is,  however,  produced  in  varying  quantity 
by  the  individual  types  of  bacteria  ;  injection  of  definite  doses  of 
some  forms  of  bacteria  and  culture  filtrates  occasioning  no  febrile 
reaction ;  some  only  after  large  doses  ;  others  causing  high  fever 
with  the  employment  of  extremely  small  amounts.  Another 
feature  to  be  considered  is  that  various  kinds  of  bacteria  known 
to  elaborate  thermogenic  substances  do  not  act  with  uniformity 
in  the  production  of  fever  in  all  kinds  of  animals,  and  different 
animals  show  even  less  uniformity  in  their  susceptibility  to  the 
fever  toxines    (Krehl)  ;   from   which  it  may  be  assumed  that  the 


Pet'cr.  169 

p\  rogenetic  substances  of  the  different  bacteria  also  liave  a 
qualitative  variation,  are  just  as  different  and  specific  as  for 
example  diphtheria  toxine  and  tetanus  toxine  (  W'assermann  I.  '1  he 
pyrogenetic  power  of  bacteria  is  not  in  any  way  related  to  their 
pathogenicit}-  (Kraus)  ;  there  are  bacteria  of  high  grade  viru- 
lence which  produce  but  little  febrile  disturbance  (as  tetanus 
bacillus),  and  on  the  contrary  there  are  non-pathogenic  microbes 
whose  cultures  nevertheless  exhibit  a  (transitory)  pyrotoxic 
activitv.  as  those  of  bacillus  prodigiosus  and  bacillus  subiilis 
(\'oges).  A  number  of  bacterial  products  when  administered  to 
the  smaller  experiment  animals  in  but  small  doses  give  rise  tO' 
increase  of  body  temperature,  while  in  large  doses  they  cause  it  to 
fall  below  normal;  and  there  is  a  notable  peculiarity  in  the  action 
of  the  substances  obtained  from  cultures  of  the  tubercle  bacilku 
and  the  glanders  bacillus,  very  small  doses  of  extracts  of  these  cul- 
tures causing  fever  to  occur  in  tuberculous  and  glanders  animals 
but  not  in  healthy  ones  (in  the  latter,  however,  a  rise  in  tempera- 
ture is  produced  when  the  extracts  are  given  in  large  doses,  which 
would  on  the  contrary  produce  depression  of  temperature  in  the 
diseased   animals   with    symptoms   of   fatal   intoxication). 

According  to  the  experiments  of  Matthes  the  sterile,  salt-free 
hydration  products  of  the  albumen  molecule,  protalbumose, 
deuteroalbumose,  peptone,  act  in  the  same  manner  as  the  last  named 
agents,  and  it  seems  that  in  the  protoplasm  of  all  living  cells 
there  exist  certain  proteid  substances  capable  of  inducing  temper- 
ature accession  when  injected  or  when  set  free  in  the  body  (Kraus, 
Wassermann).  By  subcutaneous  and  intravenous  injection  of 
blood  or  blood  serum  of  a  different  species  of  animal,  or  by  intro- 
duction of  iodide  of  potash  solution  or  pure  distilled  water  it  is 
possible  to  cause  a  rise  of  temperature,  a  phenomenon  depending 
upon  the  h^emol\tic  influence  of  these  substances,  either  the 
hemoglobin  thus  freed  or  the  fibrin  ferment  formed  occasioning 
the  increase  of  temperature.  The  injection  of  fibrin  ferment 
promptly  occasions  marked  increase  of  temperature,  true  also  of 
other  ferments  (pepsin,  rennet,  pancreatin.  invertin)  as  well  as 
of  the  animal  secretions  (milk,  urine).  The  purified  enzymes  are 
apparently  inert:  but  the  same  ferments  in  impure  state  (but 
sterile),  presumably  containing  some  albuminous  admixture,  induce 
an  elevation  of  temperature  from  which  it  may  be  inferred  that 
the  active  principles  are  some  type  of  albuminous  body  (Krehl). 
However,  the  influence  is  not  the  property  of  any  one  single  albu- 


170  Temperature  Distiirhances. 

minous  substance,  various  proteins,  bacteria  and  other  microorgan- 
isms, the  products  of  disintegration  of  red  and  white  blood  cor- 
puscles and  other  tissue  elements  all  possessing  the  same  influence. 

Foreign  albuminates  alwa_ys  give  rise  to  the  development  of 
protective  processes,  of  phagocytosis  and  the  production  of  specific, 
antibodies.  Certain  organs  like  bone  marrow,  spleen  and  lymph 
glands  are  stimulated  to  special  activity  by  the  presence  of  these 
foreign  substances  manifesting  cellular  hyperplasia  (mitotic  nuclear 
figures)  and  probably  producing  special  secretions.  This  increase 
of  their  physiological  activity  is  necessarily  associated  with 
increased  metabolism  and  the  latter  must  occasion  elevation  of 
temperature.  The  relation  between  the  production  of  antibodies 
and  febrile  attacks  is  very  striking  in  many  of  the  infectious  dis- 
eases. For  example  in  case  of  pneumonia  in  human  beings  it  is 
known  that  in  the  course  of  the  fever  protective  bodies  are  formed 
in  the  bone  marrow  and  that  the  fever  diminishes  as  these  sub- 
stances begin  to  manifest  their  bactericidal  action.  After  the  crisis 
these  protective  substances  are  found  in  considerable  amounts  in 
the  blood  (Klemperer,  Wassermann).  In  recurrent  fever  of  man 
the  onset  of  the  fever  takes  place  as  soon  as  the  organisms  appear 
in  the  blood ;  protective  bodies  are  then  formed  by  reaction  of  the 
body  cells  and  with  their  accession  to  the  blood  the  microorgan- 
isms are  destroyed  and  the  fever  falls  ;  if  these  are  removed  the 
spirilla  return  from  their  foci  of  deposit  to  the  blood  and  the  fever 
returns.  In  other  examples  the  beginning,  rise  and  fall  of  the 
fever  are  apparently  dependent  upon  definite  stages  of  develop- 
ment of  the  infectious  agents  :  in  human  malaria  the  fever  begins 
as  soon  as  the  parasites  reach  the  phase  of  sporulation  and  is 
checked  if  by  the  administration  of  quinine  the  maturation  or  rup- 
tilre  of  the  sporulating  organism  is  prevented. 

The  connection  of  fever  production  with  substances  foreign  to 
the  body  (infectious  and  toxic)  is  so  clear  that  if  an  animal  mani- 
fest febrile  symptoms  it  seems  a  permissible  conclusion  that  there 
must  be  infectious  or  toxic  substances  circulating  in  its  blood. 
Often  the  fever  is  the  only  manifestation  of  the  disease  appreciable 
during  life  to  indicate  the  existence  of  an  infection  {essential 
infectious  fever)  ;  usually  it  appears  as  a  precursor  of  other  symp- 
toms of  the  infectious  cause  {prodromal  fever),  or  accompanies 
local  or  general  disease  processes  {secondary  fever,  traumatic 
fever,  pycviiiic,  scpticcrmic,  hectic  fever,  intfannnatory  fever)  ;  and 
may  also   develop   after  the   employment   of  therapeutic   measures 


Fever.  171 

which  int;ro(hace  inrogenctic  substances  into  tlie  body  or  occasion 
their  production  in  the  system  {infusion  fever,  deprivation  fever). 
The  question  has  been  asked  whether  fever  is  useful  or  harm- 
ful to  the  body  and  whether  it  may  not  possibly  have  the  definite 
purpose  of  rendering  infectious  and  toxic  matters  harmless.     From 
the  fact  shown  b\-  various  experiments  that  temperatures  from  40  to 
42"    C.  may  inhibit  the  growth  of  a  number  of  bacteria,  attenuate 
their  virulence  or  actually  destroy   them  it  has  been   conjectured 
that  the  same  effect  is  produced  in  the  body  by  febrile  h\perther- 
mia,  that  the  fever,  "purifying  by  tire"  as  it  were,  is  in  reality  a 
factor  in  causing  recovery.     There  are  a  number  of  experiments 
which  seem  to   uphold  this   idea  :   small  experiment  animals  have 
been  showm  to  bear  better  (that  is  do  not  die  as  soon  from)   diph- 
theria, chicken  cholera  and  other  infections  if  kept  in  an  incubator 
at  41  to  42°  C.  than  when  left  in  a  lower  atmosphere.  The  resistance, 
however,  does  not  depend  upon  the  direct  action  of  the  higher  tem- 
perature on  the  microorganisms,  as  Wassermann  has  pointed  out, 
but  upon  the  fact  that  the  bod\-  when  kept  warm  is  better  able  to 
permit  the  action  of  its  natural  protective  mechanism    (phagocyt- 
osis,  antitoxine  production).     There   is  no  evidence   of  any   pur- 
pose  for  the  increased  temperature:  this  is  only  4  symptom  and 
a  result  of  the  exaggerated  metabolism,  and  the  favorable  outcome 
is  brought  about  b\    the   reactive  production  of  antibodies.     In  a 
similar  manner  the  complications  and  sequels  of  a  fever  are  not 
to  be   imputed  to   the   elevated   temperature.      C3f   course,   it   does 
cause  increased  rapidity  of  cardiac  action  and  of  respiration,  loss 
of  appetite  and  perhaps  parenchymatous  changes  :  but  the  real  point 
of  the  fever  is  in  the  severity  of  the  infection,  in  the  toxic  action  of 
the  infectious  microorganisms  which  contribute  the  real  danger,  and 
the  elevation  of  temperature  is  only  the  index  of  the  latter.     The 
restilt  of  measures  having  for  their  purpose  the  reduction  of  tem- 
perature  (cold  water  treatment    and  antipyretics)  is  not  in  conflict 
with     this     conception     of    the     relative     inutility     of     the     tem- 
perature in  fever ;  such  m^easures  manifest  their  beneficial  influence 
not  only  by  reducing  the  temperature  but  also  by  inhibiting  the 
causes  and  by  diminishing  metabolism. 

Stages  of  Fever.  The  febrile  course  is  usually  separable  into  a 
number  of  periods  or  stages.  The  inception  of  the  fever,  its  initial 
period  (pyrogenetic  stage,  stadium  incrementi^  chill  stage)  mani- 
fests itself  by  general  symptoms  of  fatigue,  weakness,  rough.ening 
of  the  hairy  coat,  loss  of  appetite  and  rise  of  the  internal  tempera- 


1^2  Temperature  Disturbances. 

ture.  In  a  number  of  affections  it  is  marked  by  cJiills  (trembling 
and  shivering  throughout  the  body )  :  during  the  paroxysm,  the 
internal  temperature_is  elevated  from  the  first  and  continues  high, 
while  the  skin  of  the  peripheral  parts  shows  a  lack  of  uniformity 
in  temperature,  the  feet,  for  example,  being  cold,  the  muzzle  in 
cattle  and  the  nose  in  dogs,  hot.  The  action  of  the  heart  is  acceler- 
ated, the  pulse  correspondingly  increased  in  frequency,  small  and 
tense ;  and  the  respirations  increased  in  number.  The  cause  of  the 
chill  is  to  be  found  in  the  spasmodic  constriction  of  the  cutaneous 
vessels  occasioned  by  the  poisonous  products  of  the  infectious 
agents:  the  loss  of  appetite  and  the  occasional  vomiting  (in  dogs) 
may  also  be  ascribed  to  a  toxic  influence  acting  upon  the  nervous 
centres  (Blumenthal ).  The  initial  or  chill  stage  lasts  for  from 
half  an  hour  to  two  hours,  or,  in  cases  where  chills  are  absent, 
for  several  days.  The  heated  stage  which  follows,  varying  in  dura- 
tion with  the  particular  disease  from  a  few  hours  to  a  number  of 
weeks,  is  that  in  which  the  temperature  elevation  reaches  its  maxi- 
mum level ;  it  is  known  as  the  fastigiiiin  or  acme  (stadium  acmeos). 
In  the  remittant  type,  characterized  by  alternations  of  depressions  of 
the  febrile  temperature  (reiiiissio)is)  and  succeeding  reaccessions 
{exacerbations ),  the  elevation  of  temperature  manifests  a  number 
of  maximal  points.  The  other  s}niptoms  keep  pace  with  the  hyper- 
thermia (loss  of  appetite,  increased  thirst,  general  weakness, 
diminution  of  the  secretions,  acceleration  of  respiration  and  pulse 
rate,  hot,  dry  skin).  The  intensity  and  duration  of  the  fastigium 
are  expressive  of  the  severity  of  the  febrile  disease,  and  estimated 
by  the  height  of  the  temperature  and  the  strength  of  the  heart's 
action.  In  a  -moderate  fever  the  temperature  should  not  rise  beyond 
40^  C. ;  an  intense  fever  is  characterized  by  an  elevation  exceeding 
40"  C.  A  fever  in  which  the  cardiac  action  is  strong  and  the  pulse 
tension  high  is  said  to  be  sthenic ;  where  the  cardiac  beat  is  weak 
and  without  force  and  the  pulse  soft  the  fever  is  spoken  of  as 
asthenic. 

In  the  period  of  febrile  decline  {stadium  dccrcmcnti  or  deferves- 
cence) the  body  temperature  returns  to  normal  and  the  associated 
symptoms  diminish  in  their  intensity.  In  case  the  fall  of  temper- 
ature takes  place  rapidly  (in  a  few  hours  or  at  the  most  within 
three  days),  sometimes  with  marked  perspiration  and  profuse 
excretion  of  urine,  it  is  spoken  of  as  crisis.  Sometimes  just  before 
defervescence  there  are  noted  special  exacerbations  of  the  febrile 
state  (perturbatio  critica) ;  incase  there  is  a  period  of  several  davs' 


Fever.  1 73 

duration  in  wliich  tlicre  is  alternation  of  notable  depression  and 
exacerbations  of  temperature  it  is  spoken  of  as  an  ainphibolic  sfai^e. 
Tlie  slow  and  Ji^radual  type  of  defervescence  is  called  lysis  or  rcsn- 
liilinn.  The  decline  of  fever  is  believed  to  be  due  to  the  tornialion 
somewhere  in  the  or^-anism  (bone  marrow,  spleen,  liver,  etc.) 
during  the  febrile  process  of  a  large  quantity  of  protective  sub- 
stances and  to  the  destruction  of  the  pyrogenetic  substances  present 
in  the  system  from  the  time  when  these  protectives  become  predomi- 
nant. Should  the  blood  become  rapidly  filled  with  i)rotective  sub- 
stances from  the  sites  of  antitoxine  j^iroductiou  or  with  |)hagocytic 
elements  from  hyperleucocytosis,  the  change  in  the  case  comes  on 
suddenly  (crisis)  in  the  first,  or  gradually  (lysis)  in  the  second 
instance.  The  termination  of  the  fever,  at  which  time  the  normal 
temperature  again  prevails  or  merely  trifling  variations  continue, 
brings  back  the  appetite ;  the  pulse  recovers  its  softness  and  even- 
ness ;  the  functions  of  all  the  organs  proceed  as  before  the  attack  : 
and  there  persist  for  a  tiiue  only  weakness  and  general  debility. 
This  is  known  as  the  period  of  convalescence.  In  case,  however, 
the  febrile  disease  go  on  to  an  unfavorable  termination,  and  there 
appear  irregular  fluctuations  in  the  temperature  curve,  a  sudden 
rise  far  above  nonual  or  a  subnormal  depression,  with  signs  of 
impending  death,  we  are  then  dealing  with  what  is  known  as  the 
premortal   [nioribund]   stage   [cf.  p.  95]. 

When  the  stages  above  mentioned  succeed  each  other  in  the 
order  indicated  the  course  of  the  fever  is  said  to  be  regular  or 
typical:  if  there  be  variations,  it  is  said  to  be  irregular  or  atypical. 

If  in  this  regular  course,  a  fever  should  continue  for  only  a  few 
hours  or  for  a  day,  the  whole  process  ending  within  this  time,  it  is 
described  as  an  ephemeral  fever.  A  fever  of  one  or  more  weeks' 
duration  with  a  temperature  curve  showing  daily  an  evening  rise 
and  a  morning  fall  comparable  to  those  of  the  nonual  body  tem- 
perature, but  at  a  level  above  that  of  the  nonual  internal  tempera- 
ture, is  said  to  be  a  continued  fever:  where  the  depressions  and 
exacerbations  are  more  pronounced  it  is  called  discontinuous  or 
remittent.  When  the  variations  in  temperature  are  so  great  that 
between  the  times  of  high  temperature  accession,  which  take  place 
periodically  (febrile  paroxysms)  Ahe^e  occur  periods  of  absence  of 
fever  (apyre.via).  the  fever  is  said  to  be  of  an  intermittent  or 
recurrent  type. 

Metabolism  in  Fever.  'J'he  causes  of  fever  are  known  to  give 
rise  as  a   rule  to  increased  destruction  of  the  albuminates,  esseti- 


174  Temperature  Disturbances. 

tially  an  increase  of  oxidation  (increased  consumption  of  oxygen). 
As  a  result  of  this  heat  production  is  increased. 

There  is,  however,  a  well  defined  type  of  fever  in  which  there  is 
no  recognizable  increase  of  heat  production  (Krehl),  the  febrile  condition 
resulting  solely  from  diminution  of  heat  dissipation. 

This  increase  exists  at  the  time  of  the  initial  stage  and  is  marked 
during  the  chill,  the  muscular  contractions  in  this  phenomenon  add- 
ing to  the  heat  production.  Heat  dissipation  is  also  increased  in 
fever;  otherwise  the  temperature  would  continue  to  progressively 
rise  throughout  the  attack  (Krehl).  Dissipation  is,  however,  less 
than  production.  (It  is  only  in  the  period  of  invasion  that  heat 
dissipation  is  with  any  uniformity  diminished,  in  the  chill,  by  the 
constriction  of  the   cutaneous   vessels.) 

The  increased  albumen  destruction  by  oxidation  is  shown  by 
the  increased  nitrogenous  output  in  the  urine,  the  increased  elimina- 
tion  of  carbonic  acid  and  the  lessened  oxygen  elimination.  Coinci- 
dently  there  is  a  retention  of  water ;  Senator  has  shown  that  of  the 
ingested  fluids,  only  one-third  or  less  appears  in  the  urine,  a  cir- 
cumstance which  cannot  be  explained  by  the  amount  lost  by  evapor- 
ation from  the  skin  (v.  Leyden).  The  water  may  be  supposed  to 
be  used  to  keep  in  solution  the  large  accumulation  of  products  of 
the  increased  metabolism  in  the  tissues  ;  this  idea  receives  corrobora- 
tion in  the  fact  that  after  the  crisis  when  the  retained  substances  are 
being  eliminated  there  occurs  a  polyuria  without  increase  of  inges- 
tion of  water  (Blumenthal).  A  large  part  of  the  nitrogen  produced 
by  the  increased  albumen  destruction  must  come  from  the  blood,  the 
disintegration  of  the  latter  being  the  cause  of  the  high  proportion 
of  potassium  and  urobilin  met  in  the  urine  (Blumenthal).  The  uric 
acid  excretion  is  also  increased,  from  which  may  be  inferred  a 
marked  destrtiction  of  the  nucleo-albumens  (Blumenthal). 

Probably  not  all  of  the  products  of  tissue  disintegration  are 
eliminated  from  the  system  or  consumed  ;  the  urine  does  not  con- 
tain everything  which  underwent  disintegration  in  the  organism. 
Probably  during  the  fever  some  of  its  products  are  employed  for 
tissue  reconstruction  or  in  the  formation  of  antitoxines.  The 
chlorides,  phosphoric  acid  and  sodium  are  found  in  the  urine  in 
smaller  proportion  than  normally.  AA'ith  the  critical  decline  of  the 
fever,  the  tissue  destruction  ceases  and  the  organism  rapidly  re- 
stores its  nitrogen-containing  structures,  the  nitrogenovis  excretion 
falling  below  its  intake  and  a  distinct  increase  in  body  weight 
ensuing    (Blumenthal).     Only  in   cases   in  which,  because  of  re- 


Fever. 


175 


sorption  of  exudates  (pneumonia),  there  is  a  large  amout  of 
nitrogen  to  be  disposed  of,  is  its  elimination  in  the  urine  main- 
tained above  the  usual  proportion.  As  the  result  of  the  degenera- 
tive changes  which  have  taken  place,  fatty  acids  appear  for  a  time 
in  the  urine  (fatty  degeneration)  ;  and  after  a  time  sodium  chloride 
may  be  again  found  in  large  amounts. 

In  all  febrile  affections  the  kidneys  are  particularly  likely  to 
be  aft'ected.  The  poisonous  bacterial  products,  and  the  substances 
of  greater  or  less  toxicity  which  come  from  tissue  destruction  are 
irritative  to  these  organs,  and  render  the  glomeruli  and  renal 
epithelial  cells  permeable  to  album.en.  As  a  rule  an  albuminuria 
of  variable  importance  is  established,  an  evidence  of  the  existence 
of  a  nephritis  of  an  exudative  type. 


lZ3A5     6'ynp)0//   12  13   /^  15  16  f?  /8 


Fig.   18. 

Continued  fever;  epidemic  pleurisy  in  a  five-year-old  horse  (after  Priedberger— 

Frolmer) . 

In  some  cases  acetone  is  found  in  the  urine,  considered  by  some 
authorities  as  indicative  of  fat  consumption,  but  regarded  by  Bknnenthal 
as  originating  from  proteid  through  bacterial  influences  and  oxidation. 
[Acetone,  diacetic  acid  and  oxybutyric  acid  are  all  occasionally  encoun- 
tered in  the  urine  in  febrile  states,  just  as  in  case  of  diabetes  mcllitus, 
and  there  is  reason  to  suppose  that  in  both  conditions  faults  of  carbo- 
hydrate metabolism  underlie  their  occurrence,  although  it  is  possible  that 
such  substances  may  in  less  direct  manner  be  products  of  fat  or  proteid 
destruction,  as  above  suggested.]  The  origin  of  diazo  bodies  (diazo 
reaction  of  urine)  has  been  attributed  (Ehrlich)  likewise  to  bacterial  influ- 
ences   (in    man    in    tuberculosis,    typhoid    fever,    measles). 

The  existence  of  fever  is  most  efficiently  detected  by  thermo- 
metric  measurement  of  the  body  temperature.  This  is  performed 
in  animals  by  introducing  a  suitable  thermometer  into  the  rectinn, 
or  in  females  into  the  vagina,  allowing  it  to  remain  for  five  minutes, 
after  which  the  degree  of  temperature  may  be  read  off.     A  single 


176 


Necrosis. 


observation  may  establish  the  presence  of  fever,  but  observations 
made  at  regular  intervals  afford  more  complete  and  certain  informa- 
tion as  to  the  existence  and  characteristic  features  of  the  fever  and 
are  necessary  in  following  its  course.  The  normal  temperature 
characteristic  of  the  animal  must  be  known,  together  with  the 
subnormal  and  hypernormal  (non-febrile)  ranges  when  in  health; 
the  differences  peculiar  to  species  and  age,  and  the  daily  physio- 
logical fluctuations.  These  are  dealt  with  in  works  on  normal 
physiology,  to  which  reference  may  be  made  (Cf.  Friedberger  and 
Frohner,  Lchrb.  dcr  kliniscJicii  UntcrsitchiDii^sinctliodcii  f.  Tier- 
ijrcfc). 

The  course  of  the  fever  can  be  luost  satisfactorily  followed  bv 


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llemittent    fever :    an    infectious    fever    in    an    eight-year-old    mare.      (After    Fried- 
berger— Frohner. ) 

recording  the  degrees  of  temperature  obtained  from  time  to  time 
by  thermometric  reading  upon  a  chart  marked  out  with  abscissa 
lines,  each  as  a  point  [with  corresponding  height  from  the  normal 
line  according  to  the  number  of  degrees  of  temperature  observed], 
thereafter  connecting  these  points  so  as  to  construct  a  scale  or 
curve  of  the  temperature  range  upon  the  chart,  the  temperature- 
or  fever-curve. 

Necrosis. 

Complete  death  of  organs  or  parts  of  organs  within  the  living 
body,  local  death,  is  known  as  necrosis  (^  viKpwais.  death)  ;  when 
this   process  of  disintegration   has   associated   with  it  the   features 


Causes  of  Xccrosis.  177 

of  degeneration  it  is  also  indicated  by  the  term  necrobiosis.  Be- 
tween the  degenerations  (the  retrograde  metamorphoses)  and  the 
necroses  it  is  impossible  to  draw  any  sharp  line  of  difference.  (There 
are  in  addition  a  number  of  other  expressions  in  use  for  the  special 
types  of  necrosis  by  which  the  death  of  a  part  in  the  living  body  is 
seen  to  occur,  which  are  often  emplo\ed  indifferently  as  synonyms — 
vide  infra).  Even  in  normal  life  in  the  interchange  going  on  in 
the  course  of  the  physiological  processes  there  is  a  certain  amount 
of  the  cellular  material  which  is  being  broken  down  in  the  tissues, 
consumed  and  replaced  by  new  cells.  The  epidermal  cells  of  the 
skin  are  continually  undergoing  keratinization.  later  desquamat- 
ing as  dead  structures,  and  newly  formed  cells  from  the  stratum 
Alalpighii  take  their  place  to  undergo  in  their  turn  the  same 
change.  In  the  same  way  the  epithelium  of  various  glands  die 
and  contribute  their  own  substance  to  their  secretions,  as  the  cells 
of  the  sebaceous  and  mammary  glands.  The  blood  cells  are  also 
perishable  elements,  some  being  all  the  time  in  course  of  disintegra- 
tion and  death,  the  formation  of  new  cells  continually  proceeding 
in  the  h?emopoietic  parts  (bone  marrow  and  lymph  glands)  to 
compensate  for  this  loss.  Other  physiological  instances  of  local 
death  are  also  seen  in  the  loss  of  the  milk  teeth  and  in  the  nnunmi- 
fication  of  the  umbilical  cord. 

Pathological  conditions  capable  of  causing  local  death  are 
usually  such  as  interfere  with  the  nutrition  of  the  cells  and  tissues^ 
and  render  the  metabolic  interchange  between  them  and  their 
surroundings  impossible.  The  most  common  is  some  interruption 
of  the  blood  supply  :  as  thrombosis  and  embolism  ( both  of  which 
occlude  the  vascular  lumen).  ru])ture  of  the  vessels,  separation  of 
the  cells  or  tissues  from  their  sources  of  supply  (traumatic,  or  the 
undermining  of  the  skin  in  case  of  subcutaneous  suppuration),  or 
compression  of  the  tissues  which  interferes  with  the  entrance  of 
blood  to  the  part.  If  the  blood  is  unable  to  gain  access  to  an 
organ  or  some  portion  of  an  organ,  no  more  than  mere  microscopic 
parts  of  it  can  be  maintained  by  the  lymph  ;  with  the  exception  of 
the  cornea  and  the  cardiac  valves,  for  which  the  lymphatic  fluid 
is  the  principal  source  of  nutrition,  no  organ  can  withstand  a  pro- 
tracted interruption  of  its  blood  supply.  This  is  especially  true 
of  gland  cells  ;  according  to  Litten  two  hours  are  sufficient  after 
ligation  of  the  renal  arteries  in  rabbits  to  cause  necrosis  of  the 
renal  epithelium,  even  though  after  removal  of  the  ligatures  the 
circulation  be  re-established.  Ehrlich  and  Rrieger  1  cited  from  Birch- 


178  Necrosis. 

Hirschfeld)  observed  a  destruction  of  the  gray  matter  as  a  result 
of  withholding  the  blood  supply  for  a  single  hour  in  case  of  the 
spinal  cord.  Interference  ^Vith  the  venous  outflow,  if  marked 
enough  to  cause  stasis  in  the  capillaries,  is  also  followed  by  nu- 
tritive disturbances  which  terminate  in  gangrene. 

The  vitality  of  the  tissues  may  also  be  overcome  by  chemical 
and  thermic  influences  producing  coagulation  or  liquefaction  of  the 
proteids  and  thus  either  directly  or  indirectly  rendering  the  pro- 
toplas^i  incapable  of  appropriating  nutrition  and  giving  off  its 
metabolic  products,  as  well  as  interfering  with  the  interchange  of 
gases  (burns,  freezing,  poisons  like  the  acids  and  alkalies,  the 
digestive  juices,  bacterial  poisons).  Evaporation  of  moisture,  as 
in  case  of  evisceration,  causes  necrosis  of  the  exposed  organs  partly 
by  drying  the  protoplasm  of  the  cells,  partly  by  desiccating  and 
stagnating  the  blood  and  lymph.  [An  important  adjuvant  cause 
of  necrosis  is  also  seen  in  the  destruction  of  innervation  of  a  part, 
as  may  be  observed  in  the  massive  and  fulminating  necrotic  changes 
met  with  in  cases  of  lesions  of  the  spinal  cord  at  points  of  pressure 
below  the  level  of  the  spinal  injury,  the  well  known  gangrenous 
decubitus  of  such  individuals.  In  some  measure  here,  disregarding 
the  important  pressure  factor,  the  necrosis  may  depend  upon 
vascular  changes  due  to  the  ner\'>ous  lesion  ;  but  there  are  reasons 
for  believing  a  more  direct  cellular  failure  results  as  well,  from 
the  loss  of  the  nervous  trophic  control.] 

As  a  general  rule  the  occurrence  of  necrosis  is  to  be  attributed 
to  a  dual  influence,  the  causative  lesion  having  both  a  direct  destruc- 
tive power  upon  the  tissue  and  at  the  same  time  interfering  with 
the  circulation  of  its  fluids. 

The  characteristics  of  necrotic  and  dying  parts  vary  with  their 
structural  peculiarities,  the  proportion  of  moisture  in  the  organ, 
the  relation  with  the  uninvolved  parts,  and  external  influences. 

Dense  structures  like  bones  and  teeth  are  subject  to  a  simple 
necrosis;  these  and  the  dense  elastic  tissues  are  extremely  resistant 
to  physical  and  chemical  agencies,  retaining  long  after  complete 
death  their  form  and  general  appearance  as  in  life.  Soft  tissues 
also,  like  the  epithelium  of  the  stomach,  if  killed  by  poisons  having 
disinfecting  power  (carbolic  acid  poisoning),  may  remain  without 
material  change,  with  but  little  alteration  of  form,  just  as  an'a- 
tomical  specimens  preserved  in  alcohol  or  formaldehyde  solutions. 
In  such  instances  the  necrosis  is  primarily  recognized  by  the  reac- 
tion in  the  surrounding  healthy  structures  in  their  effort  to  isolate 
the  dead  part   (sequestration). 


Dry  Gangrene;  Coagulation  Necrosis.  179 

Necrosis  with  desiccation  and  shrinkage  {mortiUcatio  sicca, 
mummification,  dry  g-ang'rene)  results  from  deprivation  of  moisture 
by  evaporation,  compression,  chemical  action  or  prevention  of 
the  entrance  of  iiuids  to  the  part.  A  physiological  prototype  is  ob- 
served in  the  shriveling  of  the  umbilical  cord  which  is  converted 
in  the  course  of  a  few  days  after  birth  into  a  dry  brown  parchment- 
like  mass.  On  a  small  scale  desiccation  from  loss  of  moisture  may 
be  seen  in  the  formation  of  crusts  (eschars)  on  the  surface  of 
wounds  and  ulcers,  upon  which  usually  the  exuded  tluid,  pus, 
extravasated  blood  and  a  portion  of  the  underlying  tissue  (cutis, 
mucous  membrane)  are  dried  up  into  brown  or  black. crusts  and 
scabs  (eschars  from  caustics,  scabs  of  wounds  and  ulcers).  Mum- 
mification of  deeper  and  more  extensive  type,  changing  the  tissues 
into  a  wrinkled,  brown  or  black,  tough,  leathery  material,  or  into 
a  completely  dried  hard  mass,  may  affect  the  extremities,  ears, 
feet,  tail  or  quite  frequently  the  skin,  as  the  result  of  the  action 
of  poisons  or  complete  exclusion  of  blood  from  the  part  involved, 
as  in  swine-erysipelas,  ergotism  or  occlusion  thrombosis.  A  com- 
mon example  of  this  variety  of  necrosis  is  the  leather-like  mummi- 
fication which  takes  place  in  a  dead  fcetus  retained  with  its  amnion 
in  the  uterus  in  case  the  amniotic  fluid  has  all  drained  away  or 
been  absorbed,  putrefaction  being  impossible  because  of  the  absence 
of  the  necessary  bacteria,  the  fcetus  becoming  a  veritable  mummy, 
enclosed  and  compressed  in  the  uterine  sac. 

Necrosis  with  coagulation,  coagulation  necrosis.  Where 
necrosed  tissue  assumes  the  character  of  an  albuminous  coagulate, 
being  changed  into  an  elastic,  dense,  dull  white,  grayish  yellow  or 
yellow,  and  more  or  less  dry  mass,  the  type  of  destruction  i? 
described,  following  Weigert,  under  the  term  coagulation  necrosis 
or  sometimes  caseation.  This  metamorphosis  is  peculiar  in  that 
the  dead  area  does  not  seem  diminished  or  shrunken  and  has  ap- 
parently not  suft'ered  loss  of  its  fluids,  but  rather  tends  to  be  some- 
what increased  in  volume,  projecting  slightly  above  the  surround- 
ing structures.  This  swelling  of  the  dead  tissues  depends  upon 
the  diffusion  of  Ivmph  from  the  adjacent  parts  through  the  necrotic 
substance,  saturating  it.  After  this  has  taken  place  the  coagulation 
occurs  in  the  same  wa}-  as  in  the  formation  of  a  blood  clot,  by  the 
action  of  an  enzyme  which  is  either  derived  from  the  necrotic  cells 
or  originates  from  the  primary  cause  of  the  necrosis.  This  variety 
of  necrosis  is  often  induced  by  certain  infectious  germs  (tubercle 
bacilli,   necrosing  bacilli,  bacilli   of  swine  plague)    which  seem  to 


i8o  Necrosis. 

give  off  a  ferment  into  the  tissues ;  it  is  also  frequently  seen  in 
infarcts  caused  by  embolism  and  in  new  growths  anaemic  because 
of  deprivation  of  their  blood  supply,  in  which  necessarily  it  must 
be  supposed  that  there  is  produced  by  the  tissue  disintegration 
some  substance  comparable  to  fibrin  ferment. 

The  saturation  of  a  necrosed  tissue  by  lymph  is  quite  possible  if 
evaporation  is  prevented  (for  this  reason  coagulation-necrosis  is  most 
commonly  seen  in  parts  enclosed  from  the  air,  internal  organs  and  mucous 
membranes)  ;  in  moist,  necrotic  tissue  the  blood  circulation  is,  it  is  true, 
completely  in  abeyance,  but  the  diffusion  of  the  lymph  and  the  immigra- 
tion of  lymph  corpuscles  may  be  expected. 

[Many,  among  whom  the  editor  would  include  himself,  dif- 
ferentiate between  coagulation-necrosis  and  caseation,  regarding 
the  latter  as  essentially  a  further  destructive  change,  an  advanced 
fatty  degeneration  of  the  necrotic  substance.  Where  an  area  of 
coagulation  necrosis,  or  what  is  practically  the  same  thing,  hyaline 
degeneration  (at  least  some  forms  of  the  latter),  is  retained  in  the 
tissue  and  is  not  further  disintegrated  by  liquefying  processes 
it  becomes  the  seat  of  f^tty  degeneration  and  is  broken  down  into 
a  fine  detritus,  oil  droplets,  and  often  contains  crystals  of  cholesterin 
and  fatty  acids.  When  this  is  of  advanced  degree  it  is  described 
imder  the  name  of  caseation.  Two  varieties  are  commonly  de- 
picted, dry  and  moist.  Grossly  a  dry  cheesy  focus  is  usually  de- 
fined, often  encapsulated,  whitish  or  yellowish  in  color,  of  a  friable 
or  crumbling  consistence,  reminding  one  much  of  dry  "cottage 
cheese" ;  and  imder  the  microscope  appears  as  a  uniformly  granular 
mass,  occasionally  exhibiting  a  few  persisting  fragments  of  the 
original  cellular  elements,  scattered  oil  droplets  and  crystals,  and 
when  stained  selects  diffusely  the  acid  stains  like  eosin.  A  moist 
cheesy  focus  (which  may  represent  an  area  from  which  the  moisture 
has  not  been  absorbed  or  which  may  be  determined  from  a  dry 
focus  by  imbibition  of  lymph  and  by  liquefaction  of  its  own  sub- 
stance) is  usually  not  so  clearly  defined  as  a  dry  caseated  area,  is 
paler  in  color,  softer  in  consistence  (pasty  or  mushy,  like  "cottage 
cheese"  mixed  with  milk)  ;  and  microscopically  presents  the  same 
appearance  as  mentioned  for  the  dry  variety  with  the  additional 
feature  that  usually  the  fat  globules  and  crystals  are  more  numer- 
ous. Caseation  is  especially  common  in  tuberculous  and  syphilitic 
lesions,  a  form  of  coagulation  (a  variety  of  infectious  hyalin  de- 
generation) preceding  the  fatty  change ;  it  however  may  be  met 
as  a  late  change  in  a  varietv  of  lesjons,  as  in  atherotna,  in  the  ^^.n- 


Liqiuiactiun-Xccrosis:  Moist  Goiii^rcnc.  i8l 

tents  of  a  "residual  abscess,"  etc.  The  moist  cheesy  matter  is  the 
well  known  "pyoid"  material  of  "cold  abscesses."  In  dry  casea- 
tion calcification  is  apt  to  occur  as  a  terminal  change.] 

Necrosis  with  softening,  liquefaction-necrosis.  Necrosing  tissues 
which  are  poor  in  coagulable  albuminates  but  rich  in  fat  and  fatty 
substances,  and  w^hich  contain  considerable  fluid  or  are  in  position 
to  obtain  it  from  the  entrance  of  lymph,  usually  break  down  into  a 
soft  pulpy  mass  or  into  a  milk-like  emulsion.  The  process  may 
occur  as  a  primary  one,  as  in  the  brain  and  cord,  because  of  the 
large  amount  of  myelin  contained  by  these  parts  (as  also 
seen  in  infarcts  and  haemorrhagic  effusions)  ;  or  it  may  occur 
as  a  secondary  change  where  an  originally  coagulated  necrotic  sub- 
stance becomes  macerated  after  fatty  degeneration  or  saturation 
with  serous  fluid,  or  is  softened  by  the  liquefying  products  of 
various  bacteria  (soft  caseation,  purulent  softening).  [The  type 
of  liquefaction  here  described  is  essentially  the  same  mentioned 
by  the  editor  under  the  name  of  moist  caseation  in  the  last  note. 
There  is  a  form  of  liquefaction  however  in  which  the  fatty  elements 
mentioned  by  the  author  are  absent  or  at  least  not  important,  the 
necrotic  tissues  becoming  converted  into  a  clear,  watery  fluid.  This 
resultant  fluid  may  in  a  greater  or  less  measure  be  the  product  of 
actual  conversion  of  the  solid  substance  into  liquid  ;  in  part  it  is 
made  up  of  lymph,  which  has  penetrated  the  part.  The  disappear- 
ance of  the  solid  substance  may  be  a  mere  solution  of  the  soluble 
portions  in  the  absorbed  fluid,  but  in  addition  the  insoluble  portions 
may  be  rendered  soluble  or  changed  into  fluid  by  the  influence  of 
poisons  (often  bacterial),  heat  or  cold  or  by  enzymes  originating 
in  the  necrotic  tissue  itself  or  generated  by  the  surrounding  living 
cells  or  by  microorganisms  present  in  the  mass.  Such  material 
is  apt  to  be  removed  from  the  affected  part,  usually  by  absorption, 
or  may  be  retained  within  a  capsule  as  a  cyst.] 

Necrosis  with  putrefaction,  moist  or  putrid  necrosis,  gangrene 
(^  Tct^ipaiva  ) ,  Sphacelus  (6  cr0dKe\os  from  <T<pd^€Lv ,  to  kill),  phagcdccna 
(r,  <t>a-yi^aLva) .  Whcu  uccrotic  tissuc  rich  in  fluid  is  open  to  access 
of  putrefactive  bacteria  a  putrid  decomposition  sets  in  precisely  as 
in  case  of  a  piece  of  meat  or  a  cadaver.  The  gangrenous  area  is 
soft,  pultaceous,  filthy,  dark  brown  to  green  or  dark  red  in  color, 
stinking  and  permeated  by  putrid  gases.  The  putrefactive  bacteria 
gain  entrance  from  the  surrounding  air  to  the  softened  part  through 
lesions  (from  wounds  or  ulcers)  of  its  protective  covering  (epi- 
derm,  skin)   or  from  the  canals  lined  by  mucous  membrane,  upon 


1 82 


Necrosis. 


the  surfaces  of  which'  there  is  apparently  always  present  a  rich 
variety  of  bacteria  (pharynx,  stomach  and  intestines).  The 
putrefactive  germs  may  be  carried  from  such  situations  by  the 
lymphatic  and  blood  streams  into  the  internal  organs,  where  new 
foci  of  the  putrefying  process  result  from  embolism.  Tissues  the 
seat  of  marked  hsemorrhagic  infiltration  and  those  with  large  lymph 
spaces,  are  especially  likely  to  become  gangrenous,  the  stagnating 
blood  and  rich  supply  of  moisture  favoring  the  multiplication  of 
the  putrefactive  organisms.  The  discolored  liquid  of  the  decom- 
posing part  is  known  as  putrid  icJidr. 


Fig-.    20. 

Microscopic  section  through  a  necrotic  area  in  liver  of  cow;  tlie  border  of 
the  coagulated  necrotic  material  close  to  the  normal  tissue  sliowing  a 
zone   of   cellular   infiltration. 


Microscopically,  the  principal  change  exhibited  by  necrosing  tissues 
is  the  disappearance  of  the  nuclei,  shown  especially  by  their  partial  or 
complete  loss  of  the  staining  quality  with  the  ordinary  nuclear  staining 
reagents  (hsematoxylin,  carmine  stains).  Sections  of  normal  tis.sues 
present  their  cells  and  nuclei  stained  with  clear  definition  and  distinct 
color;  necrotic  portions  look  as  though  they  were  without  nuclei,  and 
either  refuse  to  take  the  stain  or  only  assume  a  faint  diffuse  coloration. 
The   nuclear   changes   may   consist   of   a   loss   of   a   definite   outline,   accuinu- 


Symptoms  of  A'ccrosis.  183 

lation  of  the  chromatin  in  fragments  or  clumps  of  irregular  size  and 
a  variety  of  angular  or  globular  shapes  in  the  nuclear  stroma  along  the 
periphery  (karyorrliexis),  or  its  escape  into  the  cytoplasm  (pyknosis  of 
Schwann  and  Albrecht),  or  its  complete  dissolution  (karyolysis  of  Klebs). 
Besides  this  fragmentation  of  the  nuclei,  displacement  and  solution  of  their 
chromatin,  there  are  also  to  be  observed  changes  in  the  cellular  proto- 
plasm and  in  the  intercellular  substance,  resulting  in  the  loss  of  specific 
structure.  The  cell  protoplasm  and  supporting  tissue  are  changed  into 
a  turbid,  lumpy,  more  or  less  homogeneous  mass,  in  which  the  individual 
cells  can  no  longer  be  recognized.  In  case  lymph  diffusion  in  the 
necrosed  tissue  follows  and  coagulation  occurs,  the  dead  area  seems  to 
be  filled  with  apparently  •  swollen,  shining,  strongly  refractile,  fibrin-like 
masses  of  transudate  (fibrinoid  of  Albrecht  and  Schwann)  of  lumpy, 
trabecular  or  reticulate  appearance.  In  necrosis  with  softening  the  de- 
structive change  is  usually  recognized  by  the  fat  droplets  (fatty  detritus)  ; 
and  the  ichor  of  gangrenous  parts  shows,  in  addition  to  shreds  of  the 
various  tissues,  the  remnants  of  the  liquefied  red  blood  cells  in  the  form 
of  yellow  and  dark  brown  granules  and  clumps  of  blood  pigment,  and 
sometimes  such  solid  decomposition  products  as  leucin,  tyrosin,  margarin 
and  triple  phosphates,  together  with  an  enormous  number  of  putrefactive 
microorganisms. 

Symptoms  of  necrosis.  Local  death  of  tissues  causes  their  com- 
plete loss  of  functional  ability.  \Mien  the  necrosed  focus  is  of 
small  size  and  situated  in  the  midst  of  healthy  functionating  tissue 
of  the  same  type  and  having  the  same  character  of  activities, 
there  are  often  no  symptoms,  as  in  case  of  anaemic  infarcts  of  the 
kidney  and  spleen.  The  distribution  and  production  of  heat  ceases 
in  the  necrosed  part  with  the  cessation  of  the  blood  supply ;  gross 
areas  of  gangrene  on  the  periphery  of  the  body,  as  the  skin,  ears 
or  extremities,  feeling  cold.  Because  of  the  coincident  death  of 
the  sensory  nerves  within  the  gangrenous  area  the  latter  is  itself 
'analgesic,  although  the  inflammatory  reaction  at  the  periphery 
causes  sensations  of  pain.  Gangrene  in  its  inception  is  further 
recognizable  in  parts  of  the  body  exposed  to  view  by  the  dark 
brown,  dirty  dark  red  to  dark  green  discoloration,  by  the  desic- 
cation, or  by  its  putrid  odor.  In  this  latter  form,  that  is,  gangrene, 
the  parts  assume  a  doughy,  flabby  consistence;  and  if  the  gases 
cannot  easily  escape  and  accumulate  deep  in  the  meshes  of  the 
tissue  there  may  be  felt  by  light  palpation  a  crackling  {crepitation) 
of  the  breaking  or  displaced  gas  bubbles.  The  presence  of  the 
gases  gives  the  putrefying  tissue  a  bloated,  spongy  appearance,  the 
cut  surface  full  of  small  holes  (gangrenous  emphysema)  ;  together 
with  the  ichorous  fluid  these  gases  often  accumulate  under  the 
epidermis  in  cutaneous  gangrene  and  cause  the  formation  of  gan- 
grenous blebs. 


184  Necrosis. 

Ter))iiiiatwiis.  Dead  tissue  acts  upon  the  surrounding  healthy 
structures  as  a  foreign  body,  causing  both  mechanical  and  chemical 
irritation ;  in  consequence  of  which  an  inflammatory  reaction  is 
uniformly  established  in  the  adjacent  healthy  tissues.  At  the 
periphery  of  the  necrotic  part  there  may  be  observed  an  inflam- 
matory zone  marked  by  greater  or  less  inflammatory  hyperaemia 
and  accumulation  of  leucocytes.  From  the  action  of  the  fluid 
exudates  penetrating  the  dead  tissue  and  of  the  immigrated  cells 
removing  the  necrotic  substance,  partly  by  liquefaction  and  partly 
by  phagocytosis,  necrosed  parts  of  small  size  may  be  gradually 
absorbed,  especially  foci  softened  down  into  detritus  and  small 
infarcts.  At  the  site  of  the  necrosis  there  is  then  left  a  space,  a 
defect,  which  is  later  filled  in  by  proliferation  of  the  surrounding 
tissvie  or  by  inflammatory  scar  formation.  Larger  necrotic  areas, 
or  such  as  apparently  cannot  be  softened  (mummified  and  coagu- 
lated portions)  resist  absorption;  these  may  be  circumscribed  by 
the  inflammation,  encapsulated  or  completely  separated  from  the 
rest  of  the  body  {demarcation,  dcuiarcating  iiiflammatioi,  sequestra- 
tion or  circumscribed  necrosis).  In  this  way  while  the  invading" 
mass  of  leucocytes  and  other  exudates  are  softening  down  the  tissue 
at  its  borders  there  is  also  proceeding  an  inflammatory  prolifera- 
tion of  connective  tissue  and  blood  vessels  (fibroblasts,  angioplasty 
and  blood  vessel  buds)  to  the  formation  of  a  protective  wall.  If 
the  dead  material  be  situated  at  the  surface  of  the  skin  or  mucous 
membrane  it  may  be  sloughed  ofl:'  (cutaneous  slough),  and  the 
defect  repaired  either  by  subsequent  proliferation  of  the  adjacent 
tissue  or  by  cicatrization.  Necrotic  parts  situated  deeply  in  the 
body  are  surrounded  by  the  demarcating  tissues  and  come  to  be 
enclosed  in  a  dense  capsule  of  connective  tissue.  Dead  fragments 
of  bone  separated  from  their  circulatory  supply  (bone  splinters) 
are  enclosed  by  an  osteoplastic  proliferation  of  the  bone  marrow 
and  periosteum  and  thus  isolated  as  sequestra. 

In  case  the  gangrenous  foci  contain  substances  of  toxic  nature 
the  necrosis  may  assume  a  progressive  character  from  the  con- 
vection of  the  toxic  products  of  disintegration  and  putrefactive 
bacteria  by  the  invading  leucocytes  and  lymph  stream  to  other 
parts.  When  the  process  is  reproduced  in  the  immediate  vicinity 
of  the  original  focus  it  is  spoken  of  as  progressive  necrosis  or 
gangrene ;  when  the  putrefactive  organisms  are  carried  in  the  blood 
to  distant  parts,  causing  synchronously  the  same  processes  in  the 
latter,  these  new  foci  are  spoken  of  as  secondary,  metastatic  gan- 


Atrophy.  185 

greiioiis  foci,  embolic  ^i:;aiii^rciic.  A  general  putrid  intoxication 
(saf>rd'i!iia.  from  ffawpbi ,  (lecomposed,  and  ai/ia ,  blood;  mixed 
septic  intoxication  )  may  result  from  the  toxines  of  putrefymg  bac- 
teria in  the  blood  and  the  products  of  decomposition  absorbed  from 
a  gangrenous  focus ;  this  is  likely  to  run  a  fatal  course  with 
symptoms  of  fever,  collapse,  marked  cerebral  disturbances,  myo- 
cardial degeneration,  tendency  to  multiple  haemorrhage,  etc.  The 
poisons  arising  from  putrefying  matter  or  generated  by  special 
putrefactive  bacteria  have  hsemolytic  properties  and  are  paralyzant 
to  the  cardiac  ganglia  or  central  nervous  system. 

Examples  of  this  are  frequently  afforded  in  case  of  wounds  of 
the  skin  which  favor  putrid  suppuration  of  the  underlying  tissue 
(tooth  bites,  punctured  wounds  from  stable  forks),  in  putrefaction 
of  the  retained  placenta  and  gangrene  of  the  uterus,  in  intestinal 
strangulation,  deglutition  pneumonia  and  in  escape  of  the  contents 
of  the  stomach  and  intestine  in  consequence  of  perforation  of  the 
walls  of  these  organs. 

Atrophy. 

The  term  atrophy  is  employed  to  indicate  a  diminution  in  volume 
of  an  organ  or  tissue  without  essential  alteration  in  its  structure 
and  chemical  compositiori.  It  involves  a  reduction  in  size  of  the 
cells  and  tissues  (simple  atrophy)  ;  but  this  often  proceeds  to  an 
extent  that  actual  loss  of  the  cells  results  from  their  complete  re- 
gression { numerical  atrophy).  The  name  of  the  process,  derived 
from  Tp6<pos.  nourishment,  and  a  privative,  means,  precisely,  loss  of 
nutrition,  and  is  used  because  atrophy  in  the  main  is  due  to  in- 
sufficient nutrition.  This  latter  factor  may  depend  upon  the  fact 
that  the  cells  actually  do  not  receive  sufficient  nutriment  (passive 
atrophy)  or  that  they  lack  the  ability  to  appropriate  that  wdiich  is 
offered  them  (active  atrophy),  both  of  which  conditions  may  syn- 
chronously prevail  and  are  impossible  of  definite  separation  in  all 
cases. 

Atrophy  of  organs  and  their  elements  may  in  some  cases  be  a 
physiological  phenomenon,  a  part  of  the  cycle  of  their  development 
and  natural  wearing  out.  Certain  structures  dev^eloped  in 
embryonic  life  undergo  retrogression  even  before  birth  or  soon 
after,  as  the  Wolffian  bodies,  the  ductus  Botalli  and  ductus  Arantii, 
the  umbilical  vessels  and  the  thymus  gland.  In  the  period  of  most 
active  growth  the  milk  teeth  disappear  after  atrophy  of  the  dental 
pulp.     Throughout  the  entire  lifetime  there  is  a  succession  of  atro- 


i86  Retrogressive  Processes. 


i.' 


phy  of  worn  out,  aged  cells  with  replacement  by  new  and  func- 
tionally capable  cells,  as  the  protective  epithelial  cells,  glandular 
cells  or  the  blood  corpuscles.  Dependent  largely  upon  inherited 
capacity  of  length  of  life  peculiar  to  the  individual,  sooner  or  later 
a  retardation  in  the  cytogenic  energy  makes  its  appearance  as  a 
characteristic  of  old  age;  this  physiological  loss  of  tissue-forming 
power  leading  to  shrinkage  of  the  affected  parts  is  termed  senile 
atrophy.  This  is  particularly  noticeable  in  the  sexual  glands.  The 
ovaries  dwindle  after  the  discharge  of  the  ova  generated  in  early 
life ;  no  more  follicles  mature ;  the  connective  tissue  stroma  and 
tunica  albuginea  become  dense  and  the  organs  assume  a  cicatricial 
appearance.  The  testicular  epithelium  leaves  off  its  spermatogenic 
activity,  becomes  lower  and  smaller.  In  the  same  way  in  the  lym- 
phatic structures,  the  spleen,  lymph  nodes  and  bone  marrow,  the 
ability  for  cellular  proliferation  is  curtailed  and  hand  in  hand  there 
occurs  reduction  in  the  formation  of  blood  corpuscles.  Even  the 
skeletal  system  undergoes  considerable  atrophy  in  age.  the  bones  be- 
coming more  porous  and  brittle  and  lose  sensibly  in  weight ;  a  pro- 
gressive thinning  of  the  bone  trabeculse  is  especially  notable,  probably 
caused  by  increase  in  a  special  group  of  cells  (giant  cells  or  osteo- 
clasts;  6(TTiov,  bone,  and  K\a(T(reiv,  to  break)  which  are  concerned 
in  the  absorption  of  calcareous  matter.  The  ganglion  cells  of  the 
brain  become  reduced  in  size.  At  least  in  part  senile  atrophy  is  due 
to  a  physical  wearing  out,  as  when  certain  structures  become  dilated 
from  mere  loss  of  elastic  resistive  power  (elastic  fibres  which  have 
lost  their  tone  like  a  worn  out  rubber  band). 

The  following  pathological  conditions  productive  of  atrophy  are 
to  be  considered. 

I.  Lack  of  use  of  organs.  Repeated  physiological  stimula- 
tion is  essential  for-  the  preservation  of  all  cells,  keeping  cellular 
function  active  by  constant  use.  Cessation  of  this  tvpe  of  stimula- 
tion and  the  resultant  failure  of  function  are  productive  of  atrophy 
(atrophy  from  inactivity).  For  instance,  prolonged  fixation  of  a 
limb  by  skillful  bandaging  or  the  immobility  from  ankylosis  of  a 
joint  may  be  followed  by  atrophy  of  the  muscles  and  bones  of  the 
part.  As  the  stimuli  are  conveyed  by  the  nerve  tracts  it  must  be 
evident  that  disturbances  in  the  conductivity  of  the  nerves  or  loss 
of  nervous  impulse  are  especially  apt  to  occasion  atrophy  (neuro- 
pathic atrophy).  This  may  be  observed  in  palsies,  as  those  of  the 
hind  quarters  (frequently  seen  in  dogs  from  injuries  to  the  spinal 
cord),  in  which  the  musculature  of  the  hind  legs  may  be  reduced  a 


Atrophy.  187 

third  or  half  in  volume  from  the  important  loss  in  size  and  number 
of  the  muscular  fibres.  Vice  versa,  if  an  organ  to  which  they  are 
distributed  undergo  atrophy  or  be  destroyed,  the  nerves  become 
atrophic ;  the  optic  nerve  atrophies  completely  in  protracted  disease 
or  destruction  of  its  eye. 

2.  Compression.  Continual  pressure  upon  a  tissue  inter- 
feres with  growth,  hinders  the  blood  supply  to  it  and  its  lymph 
circulation,  and  directly  causes  diminution  in  the  size  of  its  cells. 
Pressure  atrophy  is  conspicuous  wherever  unavoidable,  protracted 
and  gradually  increasing  compression  of  the  tissues  obtains.  The 
renal  parenchyma  becomes  atrophic  and  eventually  as  thin  as  paper 
from  interference  wdth  the  urinary  discharge  from  the  pelvis  of  the 
kidney;  nodular  tumors  produce  depressions  in  the  tissues  in  con- 
tact with  them ;  an  iron  cavesson  makes  a  deep  groove  in  the  nasal 
bones;  a  hoof  corn  (growth  of  the  horny  hoof)  causes  a  corre- 
sponding pressure  wear  on  the  hoof  bone.  Many  facial  malforma- 
tions may  be  explained  as  the  result  of  amniotic  bands  being  wound 
about  the  jaws  in  the  process  of  development,  interfering  with  the 
further  growth  of  the  upper  and  lower  processes  of  the  first  visceral 
arch.  Cysticerci  (echinococcus,  ccei'iurus)  in  their  growth  cause 
pressure  atrophv  of  the  substance  of  the  organ  in  which  they  are 
lodged  (canurus  upon  the  brain  and  skull).  Even  the  cellular  and 
fibrillar  connective  tissue  masses  found  in  chronic  inflammation  as 
well  as  merely  a  marked  engorgement  of  the  blood  vessels  may 
serve  as  compressing  influences  upon  the  surrounding  elements ;  the 
liver  cells  atrophy  in  chronic  inflammation  of  the  hepatic  connective 
tissue  and  in  chronic  passive  congestion. 

3.  Deficient  Nutrition.  A  diminution  of  nutritive  supply 
obviously  must  occasion  atrophy  (atropliy  of  inanition) .  as  the 
tissues  can  only  retain  their  dimensions  and  energy  of  growth  when 
proper  pabulum  is  provided  them  from  the  blood.  Insufficient 
nutrition  in  diseases  of  the  digestive  organs  which  render  difficult 
the  ingestion  of  food  or  absorbtion  of  nutrition,  or  deficiency  of 
local  blood  supply,  allow  the  cells  to  waste  away.  In  starvation,  the 
fat  of  the  body  is  lost  (91  to  93  per  cent,  of  the  loss  in  weight)  ;  and 
the  musculature  (42  per  cent,  according  to  Samuel )  antl  the  cells  of 
various  organs  become  smaller.  According  to  Manawein  in  rabbits 
the  cells  of  the  liver,  which  average  22.3  micromillimeters  in  meas- 
urement, are  reduced  to  8.9  micromillimeters  in  diameter.  The 
loss  of  nutrition  is  an  associated  factor  in  pressure  atrophy  and 
neuropathic  atrophy. 


i88 


Rctvogressive  Processes. 


The  loss  of  volume  of  the  cells  in  atrophic  conditions  consists  in 
part  in  decrease  of  their  so-called  paraplastic  substances,  partly  in 
loss  of  their  actively  functionating  constituents  (Ribbert).  The 
former,  including  the  stored-up  nutrient  matter  (fat,  glycogen)  and 
the  cellular  secretory  products  (mucin),  are  generally  used  up 
without  chance  of  replacement  from  the  blood  supply  or  from  the 
protoplasm ;  the  above-mentioned  diminution  of  size  of  the  liver 
cells,  for  example,  resulting,  or  of  fat  cells  which  after  loss  of  their 


Fig-.    21. 

Fattv    infiltration    of    tlie    sural    muscles    in    pseudoliypertropliic    musouhir    atropliy ; 

X  220.      (After   Tlioma.j 


fat  are  found  shrunken  into  simple  connective  tissue  spindle  cells. 
The  functional  substance,  as  the  contractile  substance  of  muscle 
cells,  undergoes  metabolic  alterations  resulting  in  diminution  of 
its  bulk.  It  is  difficult  to  make  out  how  intercellular  substances 
come  to  undergo  the  observed  solution  and  removal,  as  it  cannot 
be  here  assumed  that  it  is  simply  carried  off  by  the  lymph,  the 
appearance  of  giant  cells  indicating  clearly  that  the  processes  opera- 
tive are  of  complicated  nature.  In  the  bone  marrow  the  presence 
and  increase  of  these  elements  seem  to  be  related  with  the  removal 


Atrophy.  189 

of  the  hard  bone  substance,  the  calcified  lamell?e  being  Hterally 
gnawed  away  by  them.  In  addition  muscle  undergoing  atroplT>'  is 
apt  to  show  proliferation  of  the  muscle  nuclei,  the  sarcolemma 
sheath  often  being  full  of  nuclei  and  giving  the  impression  of  multi- 
plication from  lack  of  tissue  pressure  (lack  of  tissue  tension)  within 
the  empty  sheath,  as  an  associated  phenomenon.  This  same  ten- 
dency to  fill  up  spaces  may  also  be  observed  in  the  fat  cells,  in 
which,  after  the  fat  has  been  used  up,  there  often  accumulates  a 
watery  or  mucinous  fluid,  giving  the  adipose  tissue  a  loose  gelatin- 
ous character  (dropsical  fat  atrophy,  often  met  in  old  horses  in  the 
epicardium).  Sometimes  succeeding  an  atrophy  in  one  tissue  a 
hypertrophy  may  take  place  in  another,  adjacent  tissue;  as  when  in 
atrophy  of  muscular  fibres  the  resulting  space  comes  to  be  occupied 
by  proliferation  of  fat  cells  (atrophia  miisculoruni  lipoiuatosa). 

The  deposition  of  the  brownish  pig-ment  granules  accompanying  vari- 
ous atrophies  (muscle,  heart,  hver,  ganghonic  nervous  cells)  is  as  yet 
not  satisfactorily  explained.  [There  is  no  doubt,  however,  that  in  most 
cases  at  least,  this  pigment  is  of  haemic  derivation,  although  the  substance 
has  been  in  some  degree  modified  by  cellular  metabolism,  and  may  there- 
fore be  spoken  of  as  autochthonous  in  conformity  with  its  usual  classifi- 
cation. It  is  a  common  feature  of  atrophic  parts,  as  might  well  be  expected, 
both  from  the  importance  of  poor  blood  circulation  as  a  causative  factor 
and  also  from  the  diminished  support  afforded  the  capillary  walls  of 
the  wasted  tissue,  that  some  degree  of  passive  hypera;niia  should  prevail; 
and  it  may  be  noted  that  the  degree  of  this  pigmentary  change  is  usually 
in   direct  relation  with  the   degree  of  such   congestion.] 

Anatomically  atrophic  parts  are  usually  characterized  by  dimin- 
ution of  volume,  poor  blood  supply  [poor  circulation,  not  neces- 
sarih-  poverty  of  amount  of  blood  present,  however],  loss  of 
their  adipose  tissue,  by  a  tough,  dry  appearance  and  by  the  assump- 
tion of  a  peculiar  grayish  tint  sometimes  approaching  a  brown  .color. 
The  general  bulk  of  the  part  may,  however,  be  maintained  by  the 
compensatory  occupation  of  the  space  caused  by  the  wasting  of 
its  proper  constituents  by  fat  or  connective  tissue.  Organs  which, 
because  of  their  situation  or  the  density  of  their  peripheral  structure, 
are  incapable  of  diminution  may.  however,  manifest  the  presence 
of  atrophy  by  loss  of  weight,  as  the  bones  and  lungs  (osteoporosis 
and  emphysema'''). 

Atrophy  invariably  causes  loss  of  function.  Atrophic  muscles 
eventually  are  incapable  of  motion;  glands  secrete  less  efficiently; 
bones  become  brittle:  nervous  structures  lose  their  irritability  and 

♦For    details    of    these    conditions    c.f.     Kitt.    Lehrb.    (J.    patliol.    Anatomie    i?- 
ffaustiere,   II.    Aufl.,    Enke.    Stuttgfirt,    1902, 


190  Retrogressive  Processes. 

power  of  nervous  conduction.  Its  consequence  to  the  life  of  the 
individual  varies  with  the  importance  of  the  affected  organ. 
Atrophy  of  one  of  the  bilaterally  situated  organs  may  be  corrected 
(compensated)  by  hypertrophy  of  the  other,  as  in  atrophy  of  one 
kidney  or  of  one  lobe  of  the  thyroid  gland. 

General  atrophy  of  the  organs  involving  the  musculature,  the 
general  fat  of  the  body  and  the  glands,  associated  with  anaemia  and 
resulting  from  general  disturbances  of  nutrition,  is  known  as 
cachexia  (i]  Kaxe^la,  a  bad  condition;  from  ij  ?|ts,  condition,  and  * 
KaKbs ,  bad),  or  when  a  phenomenon  of  old  age,  as  marasmus 
(tiapalvu,  to  fade). 

Albuminous  Degeneration  or  Cloudy  Swelling. 

Abnormal  metabolic  processes  and  lesions  of  the  cellular  proto- 
plasm may  often  manifest  themselves  by  increase  of  cellular  volume 
and  the  appearance  of  densely  packed  fine  dust-like  albuminous 
particles  in  the  cytoplasm,  with  consequent  obscuration  of  the  . 
nucleus  and  the  production  of  a  turbidity  in  the  cell  substance.  By 
treatment  with  acetic  acid  (two  per  cent.)  or  potassium  hydrate 
(one  per  cent.)  these  granules  are  dissolved  and  the  nucleus  be- 
comes clearly  visible.  Their  solution  in  excess  of  acetic  acid,  brown 
coloration  with  iodine  and  acquirement  of  a  bright  yellow  tint 
with  nitric  acid  (xanthoprotein  reaction)  indicate  the  albuminous 
character  of  these  granules.  Various  cells,  particularly  those  of 
glandular  type,  are  normally  granular,  but  as  a  rule  the  nucleus  is 
easily  made  out  and  the  cells  are  of  their  fixed  size  and  shape ; 
while  the  pathological  granulation  is  distinguished  by  the  swelling 
and  irregularity  of  outline  of  the  cells  and  by  the  loss  of  their  nor- 
mal structural  characteristics.  In  muscle  fibres,  which  show  the 
change  particularly  well,  the  transverse  striations  are  lost  and  the 
myoplasm  is  filled  with  fine  dust-like  granules  reminding  one  of 
particles  of  India  ink;  hepatic  and  renal  epithelium  looks  swollen, 
expanded  beyond  the  physiological  limits,  the  former  no  longer 
arranged  in  columns  (spoken  of  as  dissociation  by  Browicz),  the 
renal  cells  narrowing  the  uriniferous  tubules  to  occlusion. 

In  sections  this  turbidity  is  usually  not  easily  observed,  being  cleared 
up  by  the  processes  of  preparation  (alcohol,  xylol,  etc.).  The  structural 
lesion  may  also  be  inferred  in  cloudy  swollen  cells  by  the  disappearance 
of  Altniann's  granules  (bioblasts).  (Altmann  claimed  that  in  the  cells 
of  the  liver  and  kidneys  there  are  fine  granules  around  the  nucleus  ar- 
ranged in  regular  rows,  which  could  be  uniformly  demonstrated  by  certain 
staining  methods.  In  cloudy  swelling  these  granules  are  no  longer  recog- 
nizable.) 


Cloudy  SiccUijig. 


191 


This  process,  known  as  cloudy  srvelliiig,  albuiiiiiioiis  turbidity 
or  albuminous  degeneration,  first  described  by  Virchow,  occurs 
principally  as  a  result  of  toxic  influences,  both  definite  poisons 
(phosphorus,  arsenic)  and  the  toxines  of  infectious  processes 
(diphtheria,  septicaemia),  and,  too,  from  autointoxication  from  in- 
flammatory changes.  It  may  be  regarded  as  an  expression  of  dis- 
turbance of  metabolism  caused  by  such  toxic  action,  with  impair- 


A 


Fig.  22. 
A,  Cloudy  sv.-elling-;  B,  Complete  degenei-- 
ation  of  striated  muscle  fibres.  In 
B  the  middle  fibre  is  normal,  that  to 
the  left  in  early,  and  that  to  the 
right  in  advanced  degeneration; 
X  250.      (After  Perls.) 


m 


Fig  23. 
Muscle  of  horse  (htemoglobin- 
aemia,  7  hours  after  the  at- 
tack); a.  normal  fibre;  b,  tur- 
bid and  granular  fibre;  c, 
hyaline  degenerated  fibre. 
(After  Zschokke.) 


ment  of  the  elaboration  of  the  nutrient  matter  appropriated  b\ 
the  cells.  Either  the  protoplasm  is  incapable  of  assimilating  the 
albuminous  bodies  brought  to  it  and  they  therefore  accumulate  m 
undissolved  condition;  or,  as  Mrchow  assumed,  the  cell  is  in  a 
condition  of  metabolic  irritation  in  which  there  occurs  an  ex- 
cessive separation  of  its  albumens  ;  or  it  is  a  beginning  cellular  dis- 
integration with  formation  of  modified  albumens  in  the  tissue, 
which  are   with  difficulty  soluble.      [To  a  certain  extent  it   seems 


192 


Retrogressive  Processes. 


probable,  too,  that  the  swelling  of  the  cells  is  referable  to  an  ex- 
cessive presence  of  fluid,  a  cellular  dropsy.] 

Functional  disturbances  are  occasioned  by  cloudy  swelling,  well 
seen  in  the  diminished  contractile  power  in  muscle.  It  is  a  repara- 
ble process  (recognizable  in  renal  disease)  provided  the  toxic  sub- 
stances which  occasioned  the  protoplasmic  fault  are  removed. 

Anatomically  organs  which  are  affected  by  albuminous  degenera- 
tion are  usually  less  transparent  than  normally  because  of  the 
turbidity  of  their  cellular  constituents,  are  more  or  less  grayish  or 
clay-colored,  dry,  friable,  soft,  and  look  as  if  they  had  been  scalded 
or  cooked. 

The  condition  under  discussion  is  very  distinctly  met  in  the  psoas  and 
thigh  muscles  of  the  horse  in  myopathic  hemoglobinuria,  in  the  myocar- 
dium in  various  infectious  diseases  (as  pleuropnuemonia,  tetanus),  in  the 
liver  and  kidneys  in  phosphorus  poisoning. 

The  Fatty  Changes. 

The  presence  of  fat  in  the  tissues  is  a  physiological  condition 
depending  in  variable  measure  upon  the  nutrition  brought  about  by 
storage  of  the  fat  directlv  derived  from  the  food  or  formed  within 


a 


Fig.   24. 


Fatty    infiltration    of    liver    cells;    a.    normal    hepatic    cell;    b-e,    various    stages    of 
development   of  fatty   irflltralion;    X  600.      (After   Thoma. ) 

the  cells  from  the  carbohydrates  and  albumens.  Deposition  of  fat  is 
especially  seen  in  the  subcutaneous,  submucous  and  subserous  con- 
nective tissue,  in  intermuscular  septa  and  in  the  glandular  epithelium 
of  the  liver,  mammary  gland,  sebaceous  glands,  and  also  in  dogs 
and  cats  in  the  renal  epithelium.  The  affected  cells  show  the 
presence  of  fat  as  either  large  or  small  droplets ;  and  may  either 
have  normal  nuclei,  with  the  cellular  volume  varying  in  size  with  the 
amount  of  fat  present  {fat  cells,  fatty  infiltration),  or  structural 
changes  are  evident,  which  indicate  a  cellular  destruction  {fatty 
degeneration,  fatty  metamorphosis).  In  this  latter  case  the  fat  is 
frequently  found  in  innumerable  luinute.  highly  refractile  globules, 


The  Puffy  Cliaiigcs. 


193 


the  nuclei  are  obscured  or  destroyed,  and  the  ciuthnes  uf  the  cell> 
irres-ular.  The  difference  from  albuminous  ,G:ranules  may  l)e 
recognized  in  teased  preparations  by  the  f.ict  lliat  the  fat  droplets 
are  not  aft"ected  by  acetic  acid  and  alkalies,  and  in  microscopic 
sections,  which  have  been  carried  through  alcohol  and  ether, 
chloroform  or  xylol,  by  the  removal  of  the  fat  by  these  reagents, 
the  places  where  it  was  present  in  the  protoplasm  consequently  ap- 
pearing as  vacuoles   (small  holes  or  spaces — foam  structure  of  the 


Fig.   25. 

Nodular  fatty  liver  of  dog;  portion  of  a  section  under  low  magnitication.      (After 

Rauscher. ) 


cells).  An  excellent  method  of  demonstrating  the  fat  microscopic- 
ally is  by  staining  with  Sudan  III  (an  aniline  dye),  which  may 
be  employed  in  teased  tissue  or  frozen  sections  after  hardening 
with  formol,  but  not  after  the  use  of  fat  solvent  reagents,  the  fat 
droplets  being  tinged  an  orange  yellow  color  by  the  dye.  Fat  may 
also  be  fixed  by  osmic  acid,  which  makes  it  black  and  renders  it 
insoluble  in  alcohol,  ether  and  chloroform  ( it  is.  however,  still 
soluble  in  benzine,  toluol  and  xylol — Diirk). 

Fatty  degeneration  may  be  well  seen  in  muscle  fibres,  in  which 


194 


Retrogressive  Processes. 


the  transverse  stride  are  lost  and  the  substance  found  thickly  beset 
by  fine  fat  globules.  Complete  cellular  destruction  by  fatty  de- 
generation is   shown  by  the   fact  that  finally  nothing   of  the  cell 


..-.?f!Pii!&%>. 


"^iJliF 


Fig.   26. 

Fat    crystals    (so-called    margari-c    acid   needles);    X  250.      (After    Perls.) 

protoplasm  remains  but  a  mass  of  fat  globules  {fotty  granular  mass, 
fatty  detritus,  from  deter  ere,  to  disintegrate ;  [also  often  known 
as  compound  granule  cells]).  Where  the  fatty  metamorphosis 
is    further    advanced    crystallization    of    part    of    the    fat    in    the 


Fig.    27. 
Cholesterin   plates    (after  Perls) ;    X  250. 


TIic  Faftv  Chaiii'cs. 


195 


pulpv  fatty  remnants  of  the  tissue  may  take  place;  these  fat 
crystals  form  clusters  of  needles.  a])parently  not  rigid,  but  seem- 
inglv  easily  bent  ( margaric  acid  crystals),  or  may  appear  in  the 
form  of  thin  ])lates  w  ith  their  corners  broken  out  and  superimposed 
upon  one  another  in  a  step-like  fashion  (cliolcstcriii  plates,  turning 
red  with  the  addition  of  sulphuric  acid,  and  upon  further  addition 
of  iodine  taking  a  violet  or  blue  color). 

The  difference  between  fatty  infiltration  and  fatty  degeneration 
as  well  as  their  genesis  (whether  the  fat  present  in  the  cells  is 
derived  from  the  fat  brought  to  them  or  is  produced  by  a  local 
splitting  process)  is  in  most  cases  impossible  of  determination; 
sometimes  even  the  microscopic  picture  is  confused  and  even  in 
undoubted  infiltration  the  cellular  protoplasm  may  exhibit  appear- 
ances of  alteration.  ^loreover.  it  is  often  impossible  to  tell  whether 
the  destruction  of  the  cell  was  brought  about  by  the  fat  accunuila- 
tion,  or  because  of  some  special  aft'ection  of  the  cell  itself  and  the 
fat  in  the  latter  case  merely  an  associated  or  resultant  phenomenon 
of  the  destructive  change. 
Theoretically  a  dift'erence 
may  exist  in  the  proportion 
of  moisture  retained  in  the 
tissue.  In  fatty  infiltration 
the  water  is  forced  out  of  the 
tissue  and  may  fall  to  below 
50  per  cent. :  while  in  fatty 
degeneration  the  proportion 
of  water  in  the  tissue  (75  to 
78  per  cent.)  remains  normal 
(Perls).  In  fatty  infiltration 
the  addition  of  fat  to  a  liver 
may  sometimes  be  so  marked 
that  it  exceeds  40  per  cent. ; 

while  the  fatty  degenerated  organ  scarcely  ever  contains  more  ^hm 
8  per  cent.  (Perls). 

It  remains,  therefore,  a  disputed  question  whether  the  fat  is 
formed  by  cellular  function  or  whether  it  is  entirely  derived  from 
the  food  and  is  hence  only  transported  fat.  Undoubtedly  the  supply 
of  fat  or  carbohydrates  plays  an  important  part  both  in  physiological 
and  pathological  fatt\'  degeneration.  The  studies  of  Rosenfeld 
indicate  that  in  experimental  fatty  degeneration  of  the  liver,  the 
fat    of    this    organ    is    not    necessarily    produced    therein,    but    is 


I'attj-  degeneration  of  liver  cells :  a.  liver 
"cell  of  a  man  dead  from  acute  phos- 
phorus poisoning,  in  physiological  salt 
solution  ;  b.  the  same  after  removal 
of  the  fat  hy  alcohol  and  oil  of 
origanum ;  c,  fattj'  degenerated  liver 
celf  of  a  woman  dead  from  septico- 
p.vjpmia,  in  physiological  salt  solu- 
tion;   X  600.      (After  Tliom.-i.) 


ig6  Rctrogrcssiz'c  Processes. 

brought  to  the  hver  (via  blood  or  lymph)  after  removal  from 
oth^r  parts  of  the  body  (subcutaneous  tissue),  because  when 
sheep- fat  was  injected  subcutaneously  it  later  appeared  in  the  liver 
and  formed  the  principal  part  of  the  fat  of  this  organ. 

Outside  the  body  fat  may  be  produced  from  proteid,  as  shown 
by  the  investigations  of  \'oit,  Pettenkofer  and  \"irchow.  Examples 
are  met  with  in  the  formation  of  a  peculiar  wax-like  substance 
known  as  adipocere  (adeps,  fat,  and  eera.  wax)  in  corpses,  a  fatty 
change  taking  place  in  those  parts  of  the  body  lying  in  water  or 
moist  earth,  as  the  result  of  which  they  acquire  a  spermaceti-like 
nature  :  in  fatty  transformation  of  fat-free  pulmonary  tissue  pre- 
served in  water  (E.  \'oit)  ;  in  the  possibility  of  fattening  animals  on 
purely  proteid  diet  (\^oit,  Pettenkofer,  Cremer).  Pfliiger  doubts, 
however,  whether  in  the  body  fat  is  formed  from  proteid  decomposi- 
tion. [The  prevailing  opinion  is  that  direct  transformation  of  pro- 
teid into  fat  does  not  occur,  and  that  when  this  is  apparently  the 
case,  as  in  the  author's  examples,  there  are  intervening  stages  or  spe- 
cial causes.  Thus  glycogen  may  be  formed  from  proteid  by  metabolic 
changes  and  the  possibility  of  fat  production  from  this  polysac- 
charid  must  be  apparent;  or  bacterial  agency  may  be  assumed  in 
many  instances.  The  substance  of  the  bacteria  may  here  be  held 
a  possible  source  of  fat.  and.  too,  their  enzymes  seem  capable  of 
splitting  the  proteid  molecule,  with  possible  ultimate  fat  formation. 
In  one  of  these  indirect  modes  it  may  be  accepted  that  fat  may  be 
produced  from  proteid ;  and  to  whatever  degree  these  may  apply  to 
pathological  changes  in  the  living  body  it  may  be  held  that  the  fat 
in  question  may  have  had  an  original  proteid  origin. 

There  is  another  possibility,  related,  it  is  true,  with  the  following 
paragraph,  but  not  distinctly  indicated  by  Professor  Kitt,  which 
should  be  held  as  a  possible  explanation  of  the  appearance  of  fat 
in  fatty  degenerated  cells.  Fat  combined  in  the  general  protoplas- 
mic molecule  may  exist  without  being  visible  ;  in  case  of  disintegra- 
tion of  the  protoplasm  this  combined  fat  may  be  set  free  and  be- 
come apparent. 

And  at  last  from  the  standpoint  of  application  to  the  clinical 
importance  of  the  case,  the  really  important  point  is  not  so  much 
the  discovery  of  the  fat  in  the  cell  as  it  is  the  fact  that  the  cell 
is  undergoing  a  disintegrating  process — and  it  is  this  which  should 
always  be  kept  in  mind.  Whatever  be  the  theoretical  claims  for 
considering  fatty  infiltration  and  fatty  metamorphosis  together, 
the  student  should,  for  practical  purposes,  hold  them  clearly  sep- 


The  Fatty  Changes.  197 

arated.  infiltration  as  a  relatively  unimportant  accumulation  of  fat 
from  deposition,  the  fatty  degeneration  as  a  serious  and  eventually 
fatal  process  of  disintegration  with  the  appearance  of  fat,  for  one 
reason  or  another,  in  the  degenerative  protoplasm.] 

Ribbert  declares  that  the  pathological  essence  of  fatty  metamor- 
phosis is  to  be  sought  in  the  fact  that  the  cells  have  undergone  a 
retrograde  change  which  renders  them  incapable  of  further  dealing 
with  the  fat  obtained  from  the  blood,  or  that  the  cells  actually 
synthesize  the  carbohydrates,  and  possibl)'  the  albumen  api^ropriated 
from  the  blood,  into  fat,  but  cannot  further  deal  with  it,  so  that  it 
is  not  oxidized  and  remains  unchanged.  According  to  this  view  the 
process  is  essentially  one  of  disturbance  of  metabolism.  The  rela- 
tion between  pathological  fatty  degeneration  and  metabolic  faults 
is  apparent,  moreover,  in  the  fact  that  it  is  especially  likely  to  occur 
whenever  the  processes  of  oxidation  are  impaired  in  the  body ;  as 
in  all  disturbances  accompanied  by  diminution  in  the  red  cells  or 
in  the  haemoglobin  of  the  blood,  the  means  of  oxygen  distribution ; 
in  general  olig?emia  caused  liy  blood  loss  or  affections  of  the  alimen- 
tary tract ;  in  parasitic  anremias  and  in  local  aucemias  ;  in  the  fatty 
changes  commonly  resulting  from  imperfect  vascularization  and 
its  accompanying  local  anaemia,  particularly  in  rapidly  growing 
tumors  (carcinoma  and  sarcoma).  Destruction  of  the  erythrocytes 
and  consequent  diminution  of  the  oxygen  content  of  the  blood,  or, 
too,  reduction  in  oxygen  appropriation  by  the  cells  of  a  tissue  be- 
cause of  some  alteration,  may  result  from  various  toxic  causes ; 
in  these  there  arise,  as  important  or  associated  lesions,  fatty  de- 
generation of  the  liver,  kidneys,  myocardium  and  other  structures. 
If  sets  in  with  especial  intensity  and  rapidity  in  phosphorus  poison- 
ing, in  which  the  liver  is  usually  dift"usely  degenerated  (phosphorus 
liver),  in  poisoning  with  arsenic,  antimony,  iodoform,  phenol  and 
in  severe  biliary  intoxication  of  the  blood  (icterus).  Bacterial 
toxines  in  the  circulating  blood  in  infectious  diseases  likewise  occa- 
sion this  metamorphosis. 

In  regard  to  excess  of  fat  in  the  tissue  there  does  not  obtain 
any  sharp  limit  between  the  physiological  and  pathological  grades. 
"Marked  general  increase  of  adipose  cells  gives  rise  to  a  condition 
of  corpulence  or  obesity  (ob-edere,  to  eat  up),  adipositas  (adeps. 
fat)  or  lipomatosis  {  x/ttos,  fat).  Peculiarities  of  metabolism  here, 
too,  are  essential  basic  factors,  occurring  in  individuals  both  as 
congenital  and  acquired  faults  and  arising  after  atrophy  of  the 
sexual  glands  or  after  castration. 


198  Rcfrogrcssiz'c  Processes. 

According  to  the  experiments  of  Lowy  and  Richter,*  there  is  con- 
siderable diminution  in  oxidation  power  connected  with  atrophy  of  the 
sexual  glands.  The  authors  found  that  in  bitches,  seven  weeks  after 
castration,  the  consumption  of  oxygen  for  each  kilo,  of  body-weight  was 
reduced  about  twenty  per  cent.,  and  in  spite  of  increase  in  body  weight 
the  total'  gas  interchange  decreased  about  nine  per  cent.,  a  reduction 
followed  up  to  about  twelve  months  after  operation ;  in  castration  of 
males  the  diminution  of  gas  exchange  set  in  within  but  a  few  days. 
Inasmuch  as  this  loss  is  immediately  removed  by  feeding  ovariin  to 
females  and  spermin  and  didymin  to  males  after  castration,  and  the 
same  disturbances  recur  after  stopping  the  administration  of  these  sub- 
stances, it  may  be  assumed  that  the  sexual  glands  possess  a  chemical 
function    in    connection    with    metabolism. 

When  obesity  is  referable  to  an  especially  rich  stipply  of  fat 
or  fat-forming  substances  animals  are  said  to  be  "fattened"  (dietary 
obesity,  obesifas  ex  aliuieiitis).  It  is  well  known  that  this  is  favored 
by  repeated  venesection ;  the  lowering  of  gaseous  exchange  from 
the  removal  of  blood  corpuscles  may  be  a  factor  in  this  case. 

Local  acctunulations  of  fat  in  the  vicinity  of  atrophic  tissues 
are  found,  filling  in  the  spaces  left  through  the  atrophy,  as  in  atrophy 
of  the  nmscles  and  kidneys   (fat  hypertrophy  ex  vacuo). 

[Anatomically  a  part,  as  the  liver,  which  is  the  seat  of  fatty 
infiltration,  is  apt  to  be  of  a  light  yellowish  color,  enlarged,  its 
capsule  tense  and  smooth  and  the  margins  tending  to  be  rounded 
when  the  amount  of  fat  deposited  is  great.  It  cuts  with  lessened 
resistance  and  the  cut  surface  and  the  section  knife  are  greasy.] 
A  pathological  obesity  (which  is  progressive)  is  anatomically 
recognizable  by  the  increase  of  the  panniculus  adiposus  in  the 
subcutaneous  tissue,  the  peritonetim,  mesentery,  epicardium  and  as 
a  diffuse  extension  through  the  tissues,  as  the  muscles. 

Fatty  degeneration  is  characterized  by  a  dull  yellow,  ochre  or 
clay-colored  appearance  of  the  organs,  sometimes  by  distinct  in- 
crease of  the  volume  [typically  the  reserve  because  of  the  cellular 
destruction  which  is  taking  place],  a  pasty,  doughy  consistence  or 
friability,  a  greasy  sensation  given  to  the  hand,  and  a  greasy  de- 
posit on  the  knife  used  for  section  of  the  organ,  and  by  indistinct 
structural  marking  of  the  part.  Sometimes  the  discoloration  is  in 
streaks  or  flecks.  The  process  may  be  associated  with  cloudy 
swelling,  when  the  parts  look  as  if  they  had  been  cooked  [and  are 
apt  to  be  of  increased  vohnne  from  the  latter  degenerative  change]. 

The  pathological  significance  of  fatty  infiltration  and  of  fatty 
degeneration  depends  upon  the  extent  and  intensity  of  the  process 

♦Cited  from  Ilerm.  Ilahn.  Aiiat.  11.  i)hi/s.  Fohjecrschcln.  <1.  Kaatration.  Sitznngs- 
ber.    d.    Geaellsch.    f.    Morph.    11.    IMiys.    iu    Miinchen,    190'2,    XVIII,    Heft    1. 


Hyaline  Degeneration.  199 

and  upon  the  relative  importance  of  the  affected  tissues.  Pre- 
cisely in  the  same  way .  that  fat  in  the  adipose  connective  tissue 
cells  is  a  reserve  and  may  be  removed  from  these  cells,  there  is 
possible  a  recover}-  from  fatty  infiltration  in  case  of  these  or  any 
other  fat  containing"  element,  provided  the  cells  are  otherwise 
healthy.  Even  fatty  degeneration  is  recoverable  to  the  extent 
that  replacement  of  loss  in  affected  cells  occurs  from  remaining 
normal  cells  or  nuclei  (mitotic  nuclear  figures  have  been  found  in 
fatty  degenerated  cells  (Ribbert),  and  the  ordinary  recovery  from 
the  infectious  diseases  in  which  muscular  and  hepatic  fatty  meta- 
morphosis is  apt  to  occur  would  substantiate  this  view^).  The 
massive  increase  of  adipose  tissue  in  the  body  may  be  harmful  to 
the  rest  of  the  tissue  elements  from  the  mechanical  effects  of  dimin- 
ishing space  and  compressing  the  cells  against  each  other,  as  in 
the  heart,  where  in  case  of  excessive  fatty  infiltration  the  fat  pene- 
trates between  the  cardiac  muscle  fibers.  Liver  cells,  which  are 
the  seat  of  marked  fatty  infiltration  and  consequent  enlargement, 
compress  the  capillaries  distributed  between  the  cell  columns,  and 
in  this  way  give  rise  to  anaemia  and  its  results.  Both  cells  and 
tissues  are  rendered  softer  and  more  friable  by  fatty  degeneration 
and  this  diminution  of  resistive  power  against  mechanical  influ- 
ences may  have  serious  consequences,  as  rupture  of  a  degenerated 
liver  or  of  arteries  with  degenerated  walls  from  increased  blood 
pressure.  Advanced  grades  of  fatty  degeneration  have,  as  might 
well  be  expected,  a  serious  influence  upon  cellular  function  apart 
from  the  fact  that  this  process  is  in  itself  an  indication  of  patho- 
logical disturbance  of  the  cellular  protoplasm.  For  example,  an 
intense  fatty  degeneration  is  capable  of  decidedly  diminishing  or 
entireh.  destroying  the  contractile  power  of  muscular  fibres  (a  cause 
of  cardiac  dilatation  and  paralysis  of  the  heart).  In  exceptional 
circtmistances  the  process  may  be  distinctly  favorable  to  efforts 
to  effect  recovery,  facilitating  the  resorption  or  removal  of  in- 
jurious substances  like  tumors  or  foci  of  purulent  softening  in  the 
tissues. 

Hyaline   Degeneration. 

The  transformation  of  a  tissue  into  a  microscopically  homo- 
geneous, glassy  or  transparent,  colorless  and  highly  refractile 
coagulum  is  known  as  hyaline  degeneration.  There  are  produced 
as  a  result  of  this  change  one  or  more  types  of  albuminates,  sepa- 
rable  chemically    from    each   other   with    difficultv.    the    substance, 


200 


Retrogressive  Processes. 


hyaline  (v.  Reckling-hausen) ,  being  characterized  by  its  resistance 
to  acids,  by  being  uninfluenced  by  water,  alcohol  or  ether,  and  by 
the  fact  that  it  is  brilliantly  stained  with  acid  aniline  dyes  (eosin, 
orange)  and  with  carmine. 

This  degeneration,  or,  as  Diirk  calls  it,  homogenization,  occurs 
according  to  Ribbert  as  a  local  metabolic  disturbance,  in  which  the 
tissues  do  not  properly  use  up  the  proteid  supplied  to  them,  do  not 
assimilate  it  all  or  throw  it  off  before  it  is  completely  converted. 
Such'  substance  is  then  precipitated  all  through  the  tissue  overlying 
the  intercellular  substance  and  destroying  the  latter  and  the  cells 
themselves    (Ribbert).      Hyaline    formation    is    met    principally    in 

connective  tissue  and  the  vascular 
apparatus,  in  h^emorrhagic  and 
anaemic  infarcts,  thrombi,  false 
membranes,  in  the  areas  of  casea- 
tion and  in  the  connective  tissue 
of  tuberculous  lymph  glands,  in 
neoplasms ;  and  to  some  extent  the 
substance  occurs  as  a  secretory 
product,  as  the  hyaline  cylinders 
of  the  uriniferous  tubules. 

[A  number  of  pathologists  use 
the  term  hyaline  in  a  broad  sense 
to  include  the  entire  group  of 
changes  productive  of  a  homogen- 
eous and  luore  or  less  glass-like 
substance,  as  amyloid,  colloid  and 
mucinous  luaterial,  as  well  as  that 
above  referred  to ;  inasmuch,  how- 
ever, as  these  are  capable  of  dif- 
ferentiation from  the  substance  in 
hand,  it  seems  well  to  consider 
them  separately.  The  relation  of 
hyaline  degeneration  to  coagula- 
tion necrosis  as  intimated  by  the 
above  description  is  clear,  the  hva- 
line  change  suggesting  from  its  ap- 
pearances and  results  the  so-called 
fibrinoid  product  referred  to  in  the  discussion  of  coagulation.  Hva- 
line  substance  is,  however,  not  entirely  uniform,  and  the  result  of 
further  study  may  be  expected  to  further  dift'erentiate  it  into  a  num- 


Fig.    29. 

Muscle  of  horse  (hiPinoglnbinfPniia 
ten  days  after  attaok)  :  a.  nor 
mal  fibre;  b.  hvalino  lump.=; 
(After  Zschokke.) 


H  valine  Pc\i:;ciicratioii.  20i 

ber  of  similar  but  not  identical  albuminates.  There  are  minor  dif- 
ferences recognized  among  the  different  examples  in  the  staining 
reactions,  which  indicate  this  multiplicity,  but  as  yet  it  is  impossible 
to  indicate  a  clear  basis  of  separation.  As  a  result  of  this  uncer- 
tainty, however,  there  have  arisen  a  number  of  types  tentatively 
spoken  of  as  forms  of  hyaline  degeneration.  Thus,  the  hyaline  met 
in  dense  connective  tissues  as  scars,  walls  of  sclerotic  blood  vessels, 
etc.,  is  usually  regarded  as  the  typical  form,  the  fibrous  tissue  here 
forming  minute  or  grossly  visible  masses  of  the  glassy  transparent 
matter,  and  grossly  presenting  an  appearance  very  similar  to  hya- 
line cartilage,  the  material  being  of  about  the  same  consistency 
as  the  latter.  Another  form  is  met  in  tuberculous  and  syphilitic 
lesions  as  a  precursor  of  the  later  caseous  change  ;  it  is  spoken  of 
as  a  "necrotic  hyaline"  and  is  apt  to  exist  only  in  microscopically 
appreciable  amounts,  but  under  the  microscope  presents  the  same 
general  appearances  as  the  typical  variety.  In  muscle  a  hyaline 
change  minutely  distinguishable  by  the  uniform  alteration  of  the 
muscle  fibre  into  a  homogeneous,  glassy,  cylindmid  area  or  by  the 
formation  of  lumps  of  such  a  material  within  the  fibre,  and  occa- 
sionally extensive  enough  to  give  the  tissue,  when  grossly  examined, 
a  peculiar  boiled  appearance,  is  met  in  typhoid  fever  (Zenker's 
hyaline  degeneration)  in  man.  in  the  hsemoglobinsmia  of  horses, 
and  in  a  variety  of  infectious  diseases  and  local  inflammatory 
changes  in  muscle  in  various  forms  of  animal  life.  This  variety 
closely  resembles  coagulation  necrosis.  In  the  blood  a  variety  of 
hyaline  thrombi,  usually  minute  and  representing  the  primary  forma- 
tion of  the  clot,  is  due  to  a  fusion  of  blood  plaques  or  of  blood 
plaques  and  leucocytes  ;  and  in  old  clots  a  change  often  spoken  of 
as  "blood  hyaline,"  leading  to  more  or  less  homogenization  of  the 
cellular  and  fibrinous  constituents  of  the  clot  into  a  transparent, 
structureless  and  yellow-colored  (microscopically)  or  reddish 
(grossly)  material.  Definite  fibrinous  exudates,  as  that  of  pleurisy 
or  pericarditis,  and  that  of  false  membranes,  as  of  diphtheria, 
sometimes  undergo  a  similar  change  (exudative  hyaline),  losing 
all  the  reticular  appearance  of  the  earlier  stages  and  presenting 
uniformly  glass-like  sheets  or  bands  or  clumps  of  hyaline  matter. 
Within  tumors,  especially  sarcomata,  hyaline  matter  is  often  found ; 
in  some  of  the  sarcomata  mantles  of  the  substance  form  over  the 
blood  vessels  or  actually  involve  the  vessels  and  render  them  im- 
pervious (cylindromata).  In  various  changes  and  in  various  situa- 
tions in  the  body,  rounded,  spheroidal,  minute  masses,  often  show- 


202  Retrogressive  Processes. 

a  concentric  marking  in  section,  and  reminding  one  of  the  well- 
known  corpora  amylacea,  but  not  responding  to  amyloid  reagents, 
are  occasionally  met,  especially  along  the  blood  vessels ;  these  have 
the  appearance  of  hyaline  matter  and  are  tentatively  classed  with 
this  type  of  degeneration.  \\'ithin  the  cells  as  well  as  between 
them,  in  a  number  of  tumors  small  globular  masses  responding  to 
the  acid  aniline  dyes  and  having  a  hyaline  appearance  are  not  in- 
frequently seen  (Russel's  acid  fuchsin  bodies)  ;  they  were,  when 
first  noted,  interpreted  by  some  as  of  parasitic  nature,  but  are  now 
looked  upon  as  a  degenerated  substance.  The  same  bodies  are  not 
very  uncommon  within  the  various  cells,  as  those  of  the  liver  or 
kidneys,  in  animals  not  subjects  of  neoplasms  (intracellular 
hyaline). 

From  the  fact  that  these  and  even  other  examples  are  all  re- 
ferred to  this  process  the  confusion  in  our  prevailing  ideas  must 
be  evident.  The  term  "hyaloid"  is  often  employed  in  order  to 
evade  somewhat  this  confusion,  when  it  is  sought  to  describe  a 
clear,  uniform,  structureless  substance  suggesting  true  hyaline, 
but  not  giving  perfect  staining  reactions  and  not  corresponding 
chemically  with  amyloid,  mucinous  or  colloid   matter. 

The  cause  of  the  change  in  a  broad  sense  includes  disturbances 
of  nutrition  and  the  influence  of  local  intoxications,  but  the  details 
of  the  action  of  these  and  of  the  development  of  hyaline  and  hya- 
loid substances  are  confused  and  largely  wanting.  The  change  is 
probably  often  that  of  a  true  coagulation  necrosis;  in  some  forms 
it  involves  further  alterations  of  coagulated  matter:  in  others  it 
evidently  does  not  mean  the  necrosis  of  the  cells  involved,  but  by  its 
advance  leads  to  their  death,  and  is  thus  rather  a  true  metamorpho- 
sis. When  tissues  are  the  seat  of  this  change  in  its  complete  devel- 
opment they  are  entirely  functionless  and  dead ;  and  the  hyaline 
material  after  a  variable  time  becomes  the  seat  of  fatty  degeneration, 
usually  advancing  to  caseation  and  either  softening  or  becoming 
the  set  of  terminal  calcification.  There  is  no  evidence  that  indi- 
vidual cells  containing  small  globules  of  hyaline  substance  are 
seriously  incommoded  by  it,  although  the  part  of  the  cellular  pro- 
toplasm thus  aflfected  is  probably  useless  and  if  the  cells  be  greatly 
involved  it  is  probably  eventually  a  serious  lesion.] 

Mucoid   Degeneration. 

The  mucus  or  nmcin  which  is  secreted  by  the  mucous  glands 
of  mucous  memln-anes  and  is   normally   found   in  tendon   sheaths, 


Mucoid  Degeneration.  203 

biirsce,  synovial  membranes  and  in  notable  quantities  in  foetal  con- 
nective tissues,  is  often  produced  in  excessive  amounts  in  pathologi- 
cal conditions  and  found  in  such  quantities  in  the  matrix  of  tissues 
that  it  becomes  evidence  of  a  degenerative  process.  Increased  se- 
cretion of  mucus  from  cells  occurs  for  the  most  part  as  one  of 
the  phenomena  of  inflammatory  irritation,  the  mucus  appearing  as 
an  accumulation  of  a  ropy  fluid,  resembling  the  albumen  of  an 
egg  (mucous  catarrh  ),  sometimes  more  or  less  clouded  from  the 
admixture  of  desquamated  and  exuded  cells,  hi  connective  tissue. 
cartilage  and  bone,  the  occurrence  of  mucus  causes  a  gelatinous 
swelling,  an  appearance  suggestive  of  head  cheese. 

Under  the  microscope  mucus  may  be  recognized  as  transparent 
droplets  coalescing  into  clumps  (mucous  spheroids),  usually  having 
fairlv  definite  outlines.  The  cells  in  which  the  mucus  is  formed 
generally  swell  up  in  one  part,  the  mucin  causing  some  nuclear 
deformation  from  pressure,  flattening  it  and  pushing  it  toward 
the  base  of  the  cell  (transformation  of  cylindrical  cells  into  goblet 
cells)  ;  the  mucus  seems  to  originate  from  the  nucleus  in  the  form  of 
a  chromatic  substance  thrown  ofl:'  in  small  globules  (hyalosomes), 
which  take  a  uniform  blue  color  with  hsematoxxiin  and  respond 
to  the  xanthroproteic  test   (yellow  coloration  with  nitric  acid). 

[Mucoid  connective  tissues,  under  the  microscope,  are  typified 
by  the  gelatinous  structure  of  the  umbilical  cord,  and  present  a 
delicate  network  of  stellate  cells,  with  mucin  existing  within  the 
reticular  spaces  as  a  transparent  structureless  intercellular  sub- 
stance.] 

Physically,  mucin  is  characterized  by  swelling  in  water  and  the  diffi- 
culty of  passing  it  through  a  filter;  chemically  it  is  precipitated  in  white 
flocculi  by  the  addition  of  acetic  acid  (mucoid  softening),  but  is  not 
precipitated  by  ferric  chloride,  mercuric  chloride  and  nitrate  of  silver.  It 
is  insoluble  in  alcohol  and  ether.  There  are  apparently  a  number  of 
forms  of  mucin  ( Birch-Hirschfeld),  among  them  some  which  are  not 
thrown  down  by  acetic  acid  (pseudo-mucin,  metalbumin).  [Three  types 
are  commonly  recognized,  mucin,  pseudo-mucin  and  paramucin.  The  first 
and  second  are  usually  found  as  products  of  epithelial  cells;  the  third 
is  more  apt  to  be  met  in  mucoid  degeneration  of  connective  tissue.  I\Iucni 
and  pseudo-mucin  when  heated  with  a  mineral  acid  give  origin  to  a 
substance  capable  of  reducing  Fehling's  solution;  paramucin  will  reduce 
it  directly.  They  all,  as  ?.  rule,  take  a  blue  stain  with  hematoxylin,  but 
vary  in  their  staining  properties  with  aniline  dyes.  It  should  be  noted 
here  that  the  mucoid  cells,  really  "goblet  epithelium."  of  certain  cancers 
were  formerly  regarded  as  colloid,  and  at  present  are  often  thus  spoken  of; 
but  it  should  be  definitely  understood  that  these  so-called  colloid  cancers 
are   improperly  named,  and   should  be  denominated  mucoid  cancers.] 


204  Rctrogrcsskr  Processes. 

Mucoid  degeneration  of  tissues  should  be  considered  as  a  de- 
structive change;  but  the  increased  secretion  of  mucus  may  have 
a  favorable  influence  in  pathological  conditions,  by  the  envelopment 
of  harmful  corpuscular  agencies  and  thus  preventing  inflammatory 
irritation  (dust  particles,  bacteria  from  the  bronchial  tubes.  lar\nx, 
pharynx  and  nose). 

Colloid   Degeneration. 

Under  the  term  colloid  substances  are  included  a  number  of 
products  of  a  gelatinous,  brownish  and  tenacious  character,  remind- 
ing one  of  half-set  carpenter's  glue,  which,  like  mucus,  originate 
from  the  cells  in  "droplets,  appear  under  the  microscope  as  hyaline 
balls  and  clumps  and  are  entirely  insoluble  in  alcohol,  ether  and 
both  hot  and  cold  water.  The  substance  dift'ers  from  mucus,  how- 
ever, in  being  completely  soluble  in  acetic  acid  after  a  preliminary 
swelling.  This  substance  is  normally  found  in  the  thyroid  and 
prostatic  glands.  Hypersecretion  of  the  material  leads  to  the  forma- 
tion of  cysts  (goitre  of  the  thyroid  gland,  adrenal  cysts  in  the 
horse),  which  occasionally  attain  considerable  dimensions  (size  of 
a  fist).  [The  cause  of  the  process  is  unknown,  but  there  is  reason 
to  suspect  that  the  product  is  the  result  of  a  change  which  follows 
the  fusion  of  the  blood  coloring  matter  with  some  of  the  mucin.. 
It  involves  epithelial  structures,  commonly  the  thyroid,  but  is  not 
infrequently  met  in  the  kidneys,  adrenals,  ovaries,  the  cerebral  hy- 
pophysis and  elsewhere  in  the  body.  The  colloid  material  is  com- 
monly found  collected  in  spaces  lined  with  epithelium  (or  spaces 
which  probably  were  originally  so  lined),  as  cysts  which  range  from 
a  minute  size  to  that  of  a  walnut  or  rarely  even  that  of  a  fist.  The 
substance  is  an  albuminate  of  uncertain  and  probably  variable  com- 
position. Its  stift"  gelatinous  consistency,  brownish-yellow  color 
and  transparency,  together  with  the  other  features  above  mentioned, 
grossly  differentiate  it  from  mucus  and  the  hyaline  substance. 
Alicroscopically  the  material  is  of  a  transparent,  structureless  ap- 
pearance with  yellowish  tint,  and  typically  takes  the  acid  stains. 
When  W'ithin  the  cells  and  before  merging  with  the  general  colloid 
mass,  the  substance  is  colorless  and  appears  in  globules  and  small 
clumps,  which,  however,  eventually  fuse  homogeneously  with  the 
mass  of  colloid  in  the  acinus  or  cell-lined  space.  The  cells  thus 
affected  are  apparently  not  altered  primarily  and  are  affected  mainly 
by  the  pressure  of  the  collection  of  the  colloid  matter,  which  causes 
more  or  less  atrophy.] 


(jlvco_<:;cnic    J n/illralioii :    ^Imyloid    i'linni:;c. 


205 


Glycogenic    Infiltration. 

The  glycogen  which  is  physioloo-ically  stored  uj)  in  the  liver 
and  which  is  also  met  in  nuiscle,  kidneys,  uterus,  placenta,  cartilage, 
squamous  epithelium  and  in  all  of  the  organs  of  the  foetus,  may, 
when  circulating  in  abnormal  amount  in  the  blood  (diabetes  mel- 
litus)  be  found  in  still  cither  cells,  being  present  in  considerable 
proportions  in  such  circumstances  in  the  leucocytes  and  renal 
epithelial  cells.  It  is  also  found  in  pus  corpuscles  in  supourative 
aflfections,  and  in  tumors  of  embryonic  derivation  the  cells  con- 
tain glycogen.  This  C(  au- 
dition can  scarcely  be  re- 
garded as  a  special  degenera- 
tion, as  the  glycogen-bearing 
cells  show  no  other  features 
of  alteration.  The  glycogen 
exists  in  the  cells  merely 
in  the  form  of  globules  of 
larger  or  smaller  size,  clumps 
or  granules,  staining  l)rown 
with  iodine  and  readily  solu- 
ble  in   water    (or  saliva). 

[The  condition  known  as 
iodophilia,  met  typically  in 
septic  conditions,  is  due  to 
the  presence  in  the  leuco- 
cytes of  these  iodine  staining 
granules  of  glycogen.  This 
condition   is   demonstrable  b\ 

making  films   of  blocd   from   such   cases ;   these,   while   still   moist, 
being  allowed  to  dry  over  iodine  crystals.] 

The  condition  is  probably  only  an  unusual  metabolism,  an  ex- 
ceptionally rich  glycogen  infiltration,  in  which,  })ossibly,  as  sug- 
gested by  Ehrlich,  the  glycogen  was  uniformly  distributed  in  the 
living  cells  and  separated  in  drops  and  lumps  only  as  a  jxist- 
mortem   phenomenon. 


Fig.    30. 

Olvciigt'uic    infiltration    of    (lie    livei-    cells; 
X  1,000.      (After   Thoma.) 


Amyloid  Degeneration. 

The  name  amyloid  (aniylimi,  starch;  e/5os .  nature  of)  was  ap- 
plied by  \'irchow  to  a  substance  which  gives  a  color  reaction 
when    treated    with    iodine    and    sulphuric    acid    somewhat    similar 


2o6  Retro  o^rcssk'c  Processes 


^ ' 


to  that  of  starch  [when  treated  with  iodine  alone],  and  which  is 
found  in  the  tissues  as  the  result  of  a  special  process  of  meta- 
morphosis. 

[The  editor  is  accustomed  to  regard  the  process  not  as  a 
metamorphosis  or  true  degeneration  as  here  indicated,  but  rather 
as  an  infiltrative  process.  The  reasons  for  this  view  are,  it  is 
true,  not  absolutely  convincing,  but  are  suggestive.  The  material 
may  in  accordance  with  this  idea  be  supposed  to  exist  in  the 
blood  or  elsewhere  in  a  soluble  pre-amyloid  state  and  to  be  car- 
ried by  the  blood  to  be  deposited  in  its  favorite  seat,  the  walls 
of  arteries,  where  for  some  unknown  local  cause  it  is  precipitated 
as  amyloid  matter.  Its  common  occurrence  in  the  walls  of  arte- 
ries rather  than  those  of  veins,  its  appearance  in  masses  in  inter- 
cellular positions  Avhere  normally  there  scarcely  exists  material 
which  could  b}-  any  known  mode  of  transformation  assume  the 
size  of  the  common  amyloid  masses  (as  between  the  basement 
membrane  and  epithelium  of  the  renal  tubules),  are  the  jirincipal 
basis  for  this  opinion.] 

When  unstained,  amyloid  substance  is,  like  hyaline  or  colloid, 
of  a  glass-like,  homogeneous  appearance,  and  is  principally  found 
deposited  in  the  connective  tissue  framework  of  the  blood  vessels 
in  afifected  organs  as  lumpy,  swollen-looking,  trabecular  or  clump- 
like masses.  While,  however,  the  hyaline  above  discussed  is 
tinged  like  the  tissues  themselves  a  yellow  straw  color  by  iodine ; 
amyloid  substance  takes  a  mahogan}-brown  tint,  sometimes  with 
a  violet  tone,  and  stands  out  conspicuously  from  the  tissue.  If 
dilute  sulphuric  acid  or  zinc  chloride  be  applied  to  such  a  prep- 
aration, the  amyloid  substance  takes  on  a  deep  violet  to  black 
color ;  its  reaction  being  thus  somewhat  similar  to  that  of  starch 
granules  or  cellulose,  these,  however,  becoming  blue  directly  on 
the  application  of  iodine  alone.  Other  color  reactions,  charac- 
teristic of  amyloid  substance,  are  given  by  various  aniline  dyes  ; 
methyl-violet  staining  it  a  ruby  red,  methyl-green  a  reddish 
violet,  in  contrast  to  the  bluish  violet  or  green  color  given  the 
normal  tissues.  Amyloid  is  colored  yellow  by  nitric  acid,  indi- 
cating by  this  xanthoproteic  reaction  its  albuminous  nature. 

According  to  the  investigations  of  Kraw'kow  this  substance  is 
a  compound  of  an  albuminate  with  chondritin-sulphuric  acid. 
This  latter  substance,  to  which  the  iodine  reaction  is  mainlv  due 
(Ribbert)  is  found  normally  in  cartilage  and  elastic  tissue. 
Amyloid  material,   as   such,   does   not   exist  normally   in   any  part 


Amyloid  Infiltration.  207 

of  the  body,  but  results  from  some  disturbance  of  metabolism.  It 
woud  appear  that  a  hyaline,  which  either  does  not  respond  to 
the  above  reactions  at  all  or  only  partially,  is  a  precursor  of 
amyloid. 

Amvloid  degeneration  occurs  especially  after  protracted  sup- 
purations ;  this,  and  the  fact  that  its  deposition  mainly  takes  place 
in  the  connective  tissue  structures  of  blood  vessels  make  it 
plausible  that  some  unused  albuminate  passes  from  the  local  sup- 
purative areas  into  the  blood  and  is  deposited  by  the  latter  in 
the  tissues,  where  by  the  combination  with  the  chondritin-sulphuric 
acid  it  is  changed  into  amyloid  matter  (Ribbert).  Experimental 
production  of  amyloid  change  lends  some  weight  to  this  idea ; 
abscesses  have  been  produced  in  animals  by  injection  with 
pyogenic  bacteria  and  predisposing  chemicals  (oil  of  turpen- 
tine), and  amyloid  matter  found  in  various  organs  after  the 
abscesses  have  existed  for  a  long  time  (Ribbert).  However,  not 
everv  suppurative  process  results  in  amyloid  change ;  special 
nutritive  disturbances  are  also  required  for  its  production. 

The  process  is  far  more  commonly  seen  in  man  than  in 
animals.  In  man  it  is  an  ordinary  accompaniment  of  advanced 
tuberculosis,  aside  from  its  occurrence  in  chronic  suppurations ; 
but  it  is  usually  absent  in  this  connection  in  animals,  although  it 
has  been  observed  as  a  degenerative  accompaniment  of  tuber- 
culosis in  birds  (Leisering.  Roll,  personal  observations).  In 
horses  it  has  been  encountered  a  number  of  times,  especially  in 
the  liver  b}-   Rabe. 

Organs,  the  seat  of  amyloid  infiltration,  become  considerably 
enlarged :  their  consistence  is  changed,  becoming  dense  and 
inelastic  and  more  or  less  wax-like ;  in  section  the  tissue  is 
somewhat  transparent  and  homogeneous,  and  is  pale  from  an 
anaemia.  In  man  amyloid  livers  are  suggestive  of  such  names  as 
hacon-likc  livers,  zvaxy  livers  or  zcooden  livers:  in  the  domestic 
animals  amyloid  livers  have  a  somewdiat  different  consistence, 
the  decidedly  enlarged  organ  ( in  the  horse  reaching  eight  to 
fourteen  kilograms  in  weight)  becoming  friable,  and  therefore 
having  a  tendency  to  rupture.  In  the  spleen,  both  in  man  and 
animals  (hog.  dog),  the  process  occurs  either  as  a  diffuse  firm 
enlargement  of  the  organs  with  a  translucent  red  or  grayish  red, 
homogeneous  appearance  of  the  whole  substance  suggesting  an 
analogy  to  smoked  salmon  or  bacon  (ham  spleen,  bacon  spleen), 
or  as  a  change  limited  to  the  splenic  follicles,  which  in  this  case 


2o8  Rctrogrcssk'c  Processes. 

stand  out  like  swollen  sago-grains  (sago-sl^!ccii) .  In  the  kidney 
the  substance  is  hkely  to  be  deposited  in  the  glonieruH.  giving  in 
these  early  cases  the  appearance  of  glassy  granules ;  in  more  ad- 
vanced cases  the  whole  organ  may.  however,  become  waxy  and  firm. 
Microscopic  study  shows  very  clearl_\-  in  these  structures  the 
deposition  just  outside  the  capillaries  and  along  the  connective 
tissue  elements  of  the  larger  blood  vessels.  In  the  advanced 
stages  of  the  process  the  substance  is  seen  in  thick  homogeneous, 
bulging  and  lumpy  strands.  The  glandular  cells  and  connective 
tissue  corpuscles  generally  only  suffer  passively  by  pressure 
atrophy,  that  is,  they  do  not  themselves  become  amyloid  ;  Johne. 
however,  states  that  in  the  horse  the  liver  cells  also  become  en- 
larged, lobular  and  shining  and  lose  their  nuclei,  this  indicating, 
therefore,  their  ])articipation   in  the  process. 

Amyloid  infiltration  may  also  occur  as  a  purely  local  process, 
especially  in  the  connective  tissue  of  tumors  and  inflammatory 
thickenings  of  mucous  membranes  having  a  substructure  rich 
in  elastic  tissue,  as  in  the  growths  in  the  nasal  mucous  mem- 
branes of  horses  known  as  narioblastomata. 

Finally,  amyloid  may  be  met  in  the  form  of  concrement-like 
deposits.  The  hyaline  casts  [waxy  casts  J  forming  in  the  urinary 
tubules  in  inflammations  of  the  kidneys  sometimes  show  amyloid 
reactions ;  so,  too,  the  round  granules  made  up  of  epithelial 
conglomerations  and  showing  a  concentric  structure,  which 
are  found  in  the  prostate  in  man  and  in  old  dogs  and  oc- 
casionally in  the  ependyma  of  the  cerebral  ventricles  ( Bruck- 
miiller.  Johne).  These  bodies  are  known  as  corpora  aniyJacca  or 
versicolorata  in  case  they  are  colored  brown,  red  and  violet  by 
tincture  of  iodine  atid  sulphuric  acid  ;  and  as  corpora  flava  when 
they  are  merely  turned  yellow  with  iodine.  Because  of  the 
lack  of  uniformity  of  these  color  reactions,  and  because  amyloid 
substance  in  its  earlier  phases  exhibits  only  the  general  charac- 
teristics of  hyaline,  it  is  reasonable  to  suppose  that  albumens,  so 
modified  as  to  appear  hyaline,  are  precedents  of  the  amyloid 
material. 

The  pathological  significance  of  amyloid  degeneration  depends 
upon  the  extent  to  which  it  has  proceeded.  Small  local  deposits 
are  merely  incidental.  In  diffuse  infiltration  the  progressive 
character  of  the  process,  the  marked  increase  of  the  volume 
of  the  organ,  the  consequences  of  pressure  atrophy  on  the  paren- 
chymatous cells,  constitute  the  most  important  factors  in  pro- 
duction of  immediate  funtional  disturbance  of  the  organ. 


Pigmentation.  209 

Pigmentation. 

Autochthonus  Melanosis. — Normally  the  epithelial  cells  of 
the  cuticle,  especially  the  deeper  layers  of  the  rete  ^Malpighii,  the 
hairs  and  horns,  the  epithelium  of  various  ingrowths  from  the 
skin  (for  example,  the  mouth  in  dogs),  besides  the  pigmented 
epithelium  of  the  retina  and  many  ganglion  cells,  and  in  a  num- 
ber of  situations  the  connective  tissue  elements  (the  cells  of  the 
choroid,  sclera,  pia,  and  also  the  cutis),  contain  in  variable 
amounts  coloring  substance  in  the  form  of  _\ellow,  brown  or 
black  granules   (the  former  ha-niofusciii ;  the  latter,  melanin). 

The  origin  and  formation  of  this  pigment  are  as  yet  not  en- 
tirely clear.  The  entire  lack  of  similarity  to  blood  pigment, 
especially  the  absence  of  iron  as  a  constituent,  the  pigment  granules 
being,  however,  rich  in  sulphur  and  containing  nitrogen 
(v.  Nenski,  Sieber,  Abel,  Davids  and  Schmiedeberg),  would  in- 
dicate that  these  granules  are  transformed  from  the  albuminates 
formed  within  the  cells  as  products  of  a  peculiar  ("metabolic," 
from  fiera^dWeLv ,  to  transform,  to  change)  cellular  activity.  It  is 
not  known  whether  the  material  employed  in  the  pigment  pro- 
duction is  originally  derived  from  the  blood  or  whether  it  repre- 
sents an  excretory  substance  of  the  system  and  its  production  is 
comparable  to  the  formation  of  humus  ;  it  can  only  be  said  that 
in  the  same  way  as  in  early  foetal  life  and  tlience  onward,  forma- 
tion of  blood  coloring  matter  takes  place  from  the  influence  of 
cellular  activity,  or  as.  under  the  influence  of  light,  chlorophyl 
formation  is  a  form  of  cellular  function,  these  pigments  are  de- 
veloped within  the  cells. 

Connective  tissue  cells  have  been  noted  in  the  linman  coriuni  loaded 
with  pigment  and  capable  of  movements  which  actually  carry  the  pigment 
into  the  epithelial  ceils,  and  in  some  circumstances  carry  it  away  again 
ichro)natoplu->rcs).  This  has  been  observed  particularly  in  connection  with 
experimental  transplantations;  where  a  small  bit  of  white  skin  has  been 
grafted  upon  a  black  (negro),  after  healing  it  becomes  as  dark  as  the 
neighboring  tissue  from  the  penetration  of  chromatophores,  and  vice  versa 
in  transplanting  black  skin  upon  a  white  person,  loss  of  color  takes  place 
in  the  graft  by  convection  of  the  pigment  through  the  agency  of  the 
wandering  chromatophore  cells  to  the  lymph  glands.  (The  existence  of 
these  wandering  cells  has  been  doubted  by  Kromayer.)  According  to 
C.  Gessard,  the  black  pigment,  especially  of  melanotic  tumors,  is  produced 
from   oxidation   of   tyrosin    (by   an    oxygenating   diastase    called   tyrosinase") 

An  increased  accumulation  of  autochthonous  pigment,  a  liypcr- 
pigmentosis  or  hyperchromatosis,  occurs  in  the  human  skin  in  the 


210  Retrogressive  Processes. 

form  of  brown  or  black  patches,  as  similarly  colored  papillary 
hypertrophies  in  the  pigmented  moles  (nsevi),  freckles  (ephelides), 
liver  spots  (chloasmata),  lentigo;  and  is  also  met  in  increased 
pigmentation  of  the  cardiac  muscle,  of  the  enteric  musculature 
and  in  a  special  type  of  cutaneous  pigmentation  occurring  in  a 
general  disease  (Morbus  Addisonii).  In  some  of  the  domestic 
animals  the  congenital,  brown,  lentiginous  spots  are,  according 
to  Schindelka,  quite  common ;  the  condition  known  as  melanosis 
maculosa  in  calves  is  especially  frequent,  such  an  excess  of  pig- 
ment cells  existing  congenitally  that  spots  of  inky  blackness  may 
be  found  in  large  numbers  beneath  the  skin,  between  the  muscles, 
beneath  the  pleura  and  in  the  lungs,  in  the  epicardium,  in  the 
liver,  in  the  submucosa  of  various  mucous  membranes  and  in  the 
membranes  of  the  central  nervous  system.  In  foci  of  local  over- 
production there  may  often  be  observed  in  sheep  an  excess  of 
the  black  pigment  in  the  pia  mater.  There  is  also  seen  in  calves 
and  in  adult  cattle  rather  frequently  a  sepia-brown  to  ebony 
black  color  of  the  kidneys,  which,  from  the  studies  of  L.  Roth, 
may  be  considered  due  to  an  infiltration  of  the  epithelium  of 
the  convoluted  tubules  and  Henle's  loops  (the  thicker  limb)  with 
pigment  granules  which,  in  some  cases,  were  identified  as  melanin, 
in  others  as  biliverdin.  Unquestionably  the  pigment  of  melanomata 
or  melanosarcomata  (cf.  Tumors)  is  produced  by  metabolic  ac- 
tivity ;  the  proliferating  cells  contain  within  the  protoplasm  brown 
and  black  granules  in  thickest  profusion.  According  to  the  in- 
vestigations of  Berdez  and  Nenski  the  coloring  matter  of  the 
melanotic  tumors  is  rich  in  sulphur;  it  is  known  as  hippomclanin 
and  phymatorhasin. 

Haematogenous  Pigmentation,  Hcemochromatosis. — The  color- 
ing matter  of  the  blood,  haemoglobin,  in  all  conditions  causing 
haemolysis  or  destruction  and  washing  out  of  red  blood  cor- 
puscles, becomes  freed  from  the  cells ;  and  is  partly  distributed 
in  solution  throughout  the  fluids  and  tissues,  and  may  be  in  part 
precipitated,  as  is  indicated  by  the  pigmentation  of  the  tissues. 
In  the  event  of  large  numbers  of  red  corpuscles  undergoing 
solution  (haemolysis)  within  the  blood  passages,  as  in  various 
intoxications  and  infections  (blood  poisons,  piroplasmosis),  the 
coloring  matter  (haemoglobin  or  methsemoglobin)  is  transferred 
to  the  blood  plasma.  The  blood  becomes  lake-tinged,  and  the 
serum  obtained  after  venesection  from  the  clot  is  stained,  instead 
of   limpid   and   yellowish,    a    deep    red    (hcemoglobinmnia).      The 


Pigmentation. 


211 


dissolved  coloring  matter  may  pass  into  the  urine,  producing 
hcEmoglohiniiria  and  methcemoglobimiria,  in  which  conditions  the 
urine  assumes  a  bloody,  dark-red  or  brownish  black  appearance. 
Precisely  as  in  normal  life,  the  dead  blood  cells  and  their  remnants 
are  taken  up  by  leucocytes  and  carried  to  the  lymph  nodes,  spleen, 
bone  marrow  and  elsewhere;  in  cases  of  exaggerated  destruction 
of  the  erythrocytes  the  same  methods  of  transportation  are  car- 
ried on  in  greater  measure,  and  the  renmants  of  hsemoglobin  are 
deposited  in  the  various  organs  in  proportion  as  this  blood  refuse 
fails  of  complete  destruction.  Some  of  these  derivatives  retain 
their  iron  (hceniosidcriii),  as  shown  by  microchemical  reactions 
(blackened  by  ammonium  sulphide ;  bluish  green  color  on  addition 
of  yellow^  ferrocyanide  of  potassium)  ;  others  contain  no  iron 
(hcemoftiscin  and  bilirubi)i)  and  may  be  seen  as  yellowish  or  brown 
granules  and  clumps  or  as  a  diffuse,  rust-colored  or  yellowish  im- 
pregnation of  the  tissues. 


Hsemcglobin  crystals  from  the  blood  of  a 
dog  killed  by  chloroform  inhalation ; 
X    2.50.      (After  TTioma.) 


Fig.    32. 

IIa?matoidin  crystals  from  a 
large  centrally  softened 
blood  extravasation  in  the 
peritoneal  cavitv :  X  2.jU. 
(After  Thoma.) 


Haemorrhagic  foci  give  rise  to  very  profuse  hematogenous  pig- 
mentation, both  the  minute  extravasations  arising  by  diapedesis 
and  the  larger  haemorrhages ;  depending  upon  the  amount  of  color- 
ing matter  deposited  and  the  age  of  the  lesion  they  cause  a 
rusty,  ochre-like  to  black  or  slate-colored  discoloration  of  the 
tissues.  The  haemoglobin  at  first  diffuses  from  the  escaped  blood 
corpuscles  and  soaks  through  (is  imbibed  by)  the  tissues  in  the 
neighborhood    of   the    haemorrhagic    focus ;    the    washed    out    cor- 


212  Retrogressive  Processes. 

puscles  disintegrate  and  are  carried  off  by  other  cells,  especially 
leucocytes,  by  their  phagocytic  action.  Just  as  in  the  above-men- 
tioned intravascular  liquefaction  of  the  blood  cells,  the  haemoglobin 
in  its  freed  condition  is  changed  into  amorphous  masses  and 
granules  of  a  yellow  or  reddish-brown  color,  partly  deposited  in 
the  intercellular  substance  of  the  tissue  and  partly  taken  up  by 
leucocytes,  endothelial  and  other  cells.  Blood  extravasations  may 
also  contain  crystalline  deposits  especially  in  the  form  of  rhombic 
plates  and  needles  of  a  ruby-red  or  yelowish-red  tint,  known  as 
liccmatoidiii  (identical  with  bilirubin).  This  is  particularly  seen 
where  fluid  blood   remains   stagnant   for   a  long  time. 

Tissues  discolored  bj'  hssmosiderin  may  become  slate-colored  or  black- 
ened (formation  of  iron  sulphide,  pseudomelanosis)  in  places  where  they 
come  in  contact  with  sulphuretted  hydrogen  (in  the  intestinal  canal  after 
death,   or   in   ichorous    cavities   and   putrefying   hsemorrhagic    exudates). 

Icterus,  Jaundice. — Staining  of  the  tissues  by  biliary  coloring 
matter  is  known  as  icterus  {h  Urepo's)  \  it  occurs  as  the  result  of 
the  entrance  of  bile  or  biliary  pigment  into  the  blood  und 
fluids  of  the  body.  The  common  causes  of  such  absorption  of 
bile  are  diseases  which  occasion  obstruction  to  its  passage  to  the 
intestine,  and  therefore  result  in  a  biliary  stasis  (icterus  from 
stasis),  and  all  conditions  which  are  accompanied  by  obstruction 
or  narrowing  of  the  biliary  channels  (obstruction  from  gall  stones, 
compression  by  tumors,  swelling  of  the  mucous  lining  of  the 
passages),  providing  the  liver  tissue  meanwhile  continues  its  pro- 
duction of  bile.  (In  hepatic  diseases  which  lead  to  destruction 
of  the  liver  cells  or  to  a  lowered  production  of  bile,  of  course 
obstruction  of  the  ducts  cannot  occasion  any  jaundice  or  only 
minor  grades  of  the  symptom,  as  may  be  observed  in  distomiasis 
of  the  liver,  in  which  condition  this  feature  is  usually  absent.) 
In  case  the  bile  can  no  longer  escape  it  first  collects  in  the  bile 
capillaries.  This  may  be  observed  under  the  microscope  as  an 
engorgement  of  the  intraacinous  biliary  tubes  which  look  as  if 
actuallv  injected  with  greenish  bile  substance;  and  the  stasis  may 
be  further  traced  into  the  intercellular  secretory  alveoli  and 
tubules.  In  case  of  rupture  of  these  delicate  capillaries  the  bile 
may  gain  entrance  into  the  adjoining  lymph-spaces,  and  be  car- 
ried by  way  of  the  lymph  channels  into  the  blood  (thoracic  duct). 

At  other  times  it  probably  escapes  directly  from  the  liver  cells  into 
the  blood  capillaries ;  it  is  assumed  that  within  the  liver  cells,  in  addition 
to  the  biliary  secretary  vacuoles,  there  is  another  canalicular  system  which 
carries   urea   and   sugar   into   the   blood   capillaries.      (Nauwerk,    Browicz.) 


Pigmentation.  213 

Biliary  stasis  may  also  depend  upon  an  excessive  production 
of  the  secretion,  inasmuch  as  the  profusely  produced  bile  may 
also  be  sometimes  too  concentrated  and  thick  and  flow  with 
difficulty,  the  cells  in  consequence  becoming  clogged.  A  hyper- 
cholia  of  this  type  occurs  in  conditions  which  cause  a  marked 
destruction  of  red  blood  cells,  and  the  haemoglobin  set  free 
en  masse  is  then  worked  over  in  the  liver  and  renders  the  bile 
particularly  rich  in  its  pigmentary  matter.  It  is  possible,  too, 
that  the  bile  may  be  thickened  and  less  fluid  or  may  diffuse 
directlv  into  the  blood  vessels  because  of  disease  of  the  liver  cells. 
This  is  met  in  a  number  of  intoxications  and  infectious  diseases, 
where,  as  the  cause  of  the  jaundice  cannot  be  referred  to  a  condi- 
tion of  biliary  stasis,  it  is  spoken  of  as  a  resorption  jaundiee  or 
infectious  or  toxic  paracholia.      (Pick.) 

It  was  formerly  believed  that  the  formation  of  biliary  coloring  matter 
in  quantities  sufficient  to  cause  jaundice  could  also  take  place  outside 
the  liver,  in  the  blood;  and  a  hsematogenous  jaundice  was  spoken  of. 
From  the  studies  of  Minkowski  and  Xaunyn,  however,  it  may  be  consid- 
ered established  that,  even  in  cases  where  a  simple  increase  of  destruction 
of  erythrocytes  causes  this  symptom,  it  is  not  produced  except  with  the 
intervention  of  the  liver,  and  that  the  transformation  of  the  haemoglobin 
into  biliary  pigment  is  accomplished  in  the  liver.  Birds  jaundiced  by 
arseniuretted  hydrogen  rapidly  lost  their  icterus  after  extirpation  of  the 
liver,  and  where  the  liver  had  been  previously  ablated,  jaundice  could  not 
be  produced  in  any  degree  at  all.  [The  term  "local  hsematogenous  jaun- 
dice" is  sometimes  applied  to  the  yellowish  discolorations  of  fading  bruise 
marks;  it  is  permissible  only  in  a  general  w\ay,  and  in  precise  discus- 
sions the  pigment  must  be  understood  as  not  identical  with  the  jaundice 
pigment.  Although  there  may  be  more  or  less  hsematoidin  present,  there 
are  also  less  closely  allied  blood  pigments.] 

The  entrance  of  the  bile  into  the  blood  is  followed  by  an 
impregnation  of  all  the  tissues  to  which  the  blood  vessels  are 
distributed  with  the  biliary  coloring  matter,  this  giving  them  a 
biliary  tint  of  various  shades.  In  the  living  body  this  is  apt  to 
be  particularly  conspicuous  in  the  conjunctiva  and  sclera;  in  the 
dead  animal  the  yellow  color  is  principall}-  apparent  in  the  stib- 
cutaneous  tissues,  the  fat,  intermuscular  connective  tissue,  the 
lungs,  I'ver  and  kidneys,  the  mucous  membranes  and  their  mus- 
cular coats.  Where  the  normal  color  of  an  organ  was  pale  the 
discoloration  may  take  on  an  intense  citron-yellow  hue ;  the  dark 
liver  and  kidney  tissue  becomes  saffron  yellow  to  olive  green  or 
o-reenish-black.  Even  the  bones  as  well  as  fibrinous  blood  clots 
and  the  blood  serum  assume  a  biliary  tint.     As  the  pigment  gains 


214  Retrogressive  Processes. 

access  to  all  the  glands  their  secretions  also  become  yellowish ; 
and  the  pigment  is  especially  noticeable  in  the  urine.  [The 
saliva,  gastric  and  pancreatic  juice,  tears  and  mucus  are  apt 
to  be  free  from  coloration.]  Only  cartilage,  the  cornea  and 
the  enamel  of  the  teeth,  and,  too,  the  brain,  take  up  but  little  of 
the  color.  Because  of  the  diffuse  uniformity  of  impregnation 
of  the  intercellular  substance  and  of  the  cells  with  the  coloring 
matter,  it  at  times  is  not  noticeable  under  the  microscope  (per- 
haps washed  away  in  the  details  of  preparation  of  the  specimen)  ; 
but  in  other  instances  some  of  the  cells,  as  those  of  the  liver,  are 
stained  an  intense  yellow  or  yellowish-brown,  and  granular  and 
coarser  deposits  of  a  yellow,  brownish  or  green  color  are  found 
in  the  protoplasm,  especially  in  the  hepatic  and  renal  epithelial 
cells.  The  pigment  is  sometimes  seen  in  crystalline  form  (ruby- 
red  rhombic  plates  of  bilirubin)  in  the  kidneys,  spleen  and  bone 
marrow. 

Jaundice  may  be  a  transitory  condition ;  the  liver  after  removal 
of  the  interference  to  the  passage  of  the  bile  resuming  its 
normal  functions  and  the  resorbed  bile  being  eliminated  by  the 
urine,  etc.  In  case  of  more  prolonged  duration  faults  of  the 
organism  become  apparent.  In  the  first  place  the  absence  of  a 
sufficient  amount  of  bile  in  the  intestine  may  interfere  with  diges- 
tion; in  the  second  place  the  bile  stasis  in  the  liver  may  cause 
pressure  upon  the  liver  cells  and  can  give  rise  to  degenerative 
and  necrotic  changes ;  thirdly  the  mingling  of  the  bile  with  the 
blood  brings  into  the  latter  and  into  the  different  organs  sub- 
stances which  are  haemolytic  and  have  other  toxic  influences. 
The  biliary  coloring  matter  and,  too,  the  biliary  acids  are  to  be 
included  among  such  toxic  substances,  the  latter  undoubtedly  being 
toxic  to  the  nervous  system.  [It  is  supposed  that  the  itching 
complained  of  by  jaundiced  human  beings,  and  to  some  extent 
present  in  animals,  is  due  to  an  irritation  of  the  skin  by  the 
biliary  pigment ;  and  the  slowing  of  the  cardiac  rate  in  jaundice 
is  directly  referable  to  the  action  of  the  biliary  acids  or  their  salts 
upon  the  vagus,  or  in  marked  instances  upon  the  heart  itself.] 
Moreover,  the  influence  of  substances  produced  in  intestinal  putre- 
faction should  be  kept  in  mind,  these  materials  being  absorbed 
from  the  intestines  and  passed  through  the  diseased  liver  which 
is  no  longer  able  to  neutralize  their  poisonous  properties.  Severe 
cerebral  symptoms  developing  in  cases  of  biliary  obstruction  and 
sometimes    fatal    (convulsions,    coma,    delirium),    accompanied    by 


Pigmentation.  215 

high  fever,  indicate  the  existence  of  such  an  autointoxication, 
which  is  designated  as  icterus  gravis  and  cholcemia. 

Exogenous  Pigmentation. — When  the  tissues  are  impregnated 
with  pigmentary  substances  which  gain  access  to  the  body  from 
the  exterior  the  process  is  known  as  exogenous  pigmentation. 
"The  most  common  example  is  the  deposition  of  carbonaceous  ma- 
terial (anthracosis)  in  the  lung,  practically  always  found  in  man 
from  inhalation  of  the  particles ;  it  also  occurs  in  dogs  which 
are  compelled  to  pass  much  of  their  time  in  smoky  places, 
and  in  horses  kept  for  a  long  time  in  coal  mines.  The  in- 
haled dust,  except  that  which  is  removed  by  the  bronchial 
mucus  and  by  the  ciliary  activity  of  the  tracheal  cells,  re- 
mains suspended  in  the  alveoli  [and  smaller  tubes],  is  taken  up 
by  wandering  cells  (dust  cells)  :  part  being  carried  in 
the  pulmonary  lymph  channels  and  reaching  the  lymph  glands 
of  the  lungs  and  bronchial  tree,  part  being  deposited  in  the  lymph 
spaces  of  the  lungs.  Wirying  with  the  quantity  of  carbon  thus 
deposited,  the  lungs  and  lymph  glands  become  mottled  and  of  a 
grav    slaty    appearance   or   uniformly   and    completely   blackened.* 

Dark  pigmentations  may  also  be  caused  by  the  deposition  of 
mercurv,  lead  and  silver,  observed  som.etimes  after  medicinal 
administration  of  preparations  of  these  metals,  as  in  case  of  the 
black  color  of  the  intestinal  villi  in  the  horse  after  the  adminis- 
tration of  calomel.  It  is  usually  the  result  of  the  formation  of 
mercuric  and  plumbic  sulphides  from  contact  with  the  sulphuretted 
hydrogen  of  the  gastro-intestinal  contents.  In  employing  nitrate 
of  silver  in  internal  medication  it  is  absorbed  from  the  alimentary 
tract  and  deposited  in  extremely  fine  granules  (reduced  to  metallic 
silver)  in  all  the  different  organs,  skin,  conjunctiva,  kidneys,  etc., 
and  gives  them  a  grayish  pigmentation.  The  condition  is  known 
as  argyria. 

By  means  of  subcutaneous  and  intravenous  injections  of  staining 
solutions  (carmine,  indigo-carmine,  methylene  blue)  the  tissues  of  the  body 
may  be  colored  bUie  or  red.  The  protoplasm  of  many  cells  takes  up  the 
stain  diffusely  in  part ;  sometimes  instead  a  granular  deposition  takes  place 
from  combination  of  the  piginent  with  certain  granular  constituents  of  the 
cells    (Arnold,  Ribbert). 

[The  eff'ect  of  external  or  exogenous  pigmentation  is  usually 
trivial  aside  from  the  mere  discoloration  and  is  only  important 
when    intense   or    as    a   predisposing   cause    to    more    serious    dis- 

*For  details  cf.  Path.  Anatomie  d.  Haustiere.     II.  Aufl.   Stuttgart,  Ferd.   Enke. 


2i6  Retrogressive  Processes. 

turbances.  Each  pigment  particle  is  essentially  a  foreign  body 
and  indnces  a  certain  amount  of  inflammatory  reaction,  usually  of 
low  grade  and  productive  of  an  increased  amount  of  fibrous  tis- 
sue. Parts  the  seat  of  marked  pigmentation,  as  the  lungs  and 
bronchial  glands,  become  more  or  less  indurated.  The  possibility 
of  infection  by  tuberculosis,  especially  noted  in  man,  becomes  more 
easy  when  previous  dust  inhalation  has  induced  a  chronic  bron- 
chitis and  has  induced  the  secondary  faults  of  pulmonary  blood 
and  Ivmph  drainage  and  has  lowered  the  general  vital  resistance  of 
their  tissue  b\-  a  prolonged  chronic  interstitial  inflammation.  In 
less  important  organs  than  the  lungs,  of  course,  the  changes  occa- 
sioned by  external  pigmentary  deposit  are  proportionately  less 
serious.] 

Calcification   and  the  Formation  of  Calculi. 

Calcium  salts  are  normally  present  in  solution  in  the  body 
fluids  (calcium  glycerin-phosphate,  carbonate,  lactate,  oxalate,  etc.). 
Deposition  of  lime  in  solid  form  takes  place  normally  in  the  bones 
and  teeth  of  man  and  the  animals  ;  and  in  herbivora  there  is  nor- 
malh-  excreted  in  the  urine  such  large  amounts  of  calcium  salts 
that  by  mere  cooling  they  precipitate  and  the  urine  at  time  of 
voidance  may  even  be  turbid  from  their  presence  (horse).  Cal- 
cium impregnates  the  matrix  of  bone  and  teeth  with  so  much 
uniformity  of  distribution  that  it  is  not  apparent  in  definite  masses, 
being  recognized  only  by  the  solidity  of  the  structure  and  by 
chemical  analysis ;  in  the  urine  it  separates  as  amorphous  granular 
and   crystalline   forms. 

The  deposition  of  calcium  salts  in  other  parts  than  those  men- 
tioned is  pathological  and  is  known  under  the  names  calcification, 
cretaceous  iniiltration,  petrification  and  incrustation. 

The  basis  for  this  deposition  is  probably  to  be  sought  in  the 
removal  of  the  substances  favoring  the  maintenance  of  the  lime  in 
solution,  as  free  carbonic  acid,  and  the  transformation  of  earthy 
salts,  which  are  soluble  in  water,  into  insoluble  calcium  compounds, 
and,  too,  in  increased  supply  of  lime.  Thus,  pathologically,  calcifica- 
tion is  apt  to  occur  in  dead  or  altered  tissues  in  which  free  carbonic 
acid  exists  in  lowered  amount  and  in  which  gaseous  interchange 
by  the  cells  is  essentially  impaired,  or  may  appear  in  secretions  and 
excretions  where  it  leads  to  the  formation  of  concretions.  [Klotz 
{Jour,  of  Exper.  Med.,  1905,  vii,  p.  633)  has  recently  attempted 
to  explain  pathological  calcification  in  necrotic  degenerative  areas 


Calcification.  217 

upon  the  assumption  of  a  previous  fatty  degeneration  of  these 
structures,  soaps  of  lime  being  formed  primarily  by  combination 
of  lime  brought  in  solution  by  the  juices  permeating  the  altered 
tissues  with  the  fatty  acids.  These  soaps  are  later  further  changed 
by  substitution  of  the  fatty  acids  by  carbonic  acid  and  phosphoric 
acid.  Wells  {Jour,  of  Med.  Research,  1906,  X.  S.  ix,  p.  491)  can- 
not find  evidence  of  constant  and  important  occurrence  of  these 
soaps  as  a  stage  in  the  process,  although  in  traces  he  finds  such 
soaps  to  exist  in  areas  of  calcification.  Fischler  and  Gross  (Zieg- 
ler's  Bcitragc,  1905,  Festschrift  fiir  Arnold,  p.  326)  have  also 
found  evidence  of  the  presence  of  such  soaps  in  atheroma  and  in 
the  margins  of  infarcts,  but  not  in  caseous  areas,  and  are  unable 
to  definitely  declare  that  soap  formation  is  an  essential  stage  in 
calcification.  Wells  regards  pathological  calcification  as  probably 
essentially  similar  to  normal  deposition,  and  inclines  to  the  idea 
that  there  exists  or  is  produced  in  the  area  some  substance  having 
particular  affinity  for  calcium,  although  he  is  unable  to  indicate  its 
nature  ;  it  is  not.  however,  dependent  upon  the  vital  state,  as  in 
cartilage  it  exists  both  when  the  cartilage  is  Hving  and  after 
it  is  boiled.] 

In  distinction  from  physological  calcification,  in  which  a  perfectly 
homogeneous  combination  of  the  lime  with  the  matrix  obtains,  patholog- 
ical calcification  is  manifested  on  microscopic  examination  by  the  presence 
of  fine,  highly  refractile  granules,  looking  like  particles  of  fat  and  pig- 
ments, which,  with  direct  light  (complete  closure  of  the  ■  substage  dia- 
phragm), have  a  dull,  glistening,  whitish  appearance,  and  are  found  both 
within  and  between  the  cells.  On  the  addition  of  acids  (especially  hydro- 
chloric acid)  the  calcium  salts  are  dissolved  and  the  presence  of  calcium 
car'conate  is  indicated  by  the  immediate  effervescence  (carbonic  acid).  With 
pure  sulplniric  acid  great  numbers  of  crystals  of  gypsum  (calcium  sulphate ) 
separate  in  delicate  pointed  crystals,  scattered  all  through  the  tissue.  A 
calcified  tissue  (the  same  in  case  of  partial  calcification)  takes  a  very 
intense   dark  blue   stain   with   ha?matoxylin. 

Ossified  tissue  differs  from  merely  calcified  structures  by  the  forma- 
tion of  lamellae  of  the  matrix  (Haversian  lamcllre)  and  the  inclusion 
of  the  bone   cells   in  the   intricately   branched   lacunae. 

Petrification  of  tissues  renders  them  as  hard  as  bone  and  gives 
them  a  dirty  white  appearance.  As  a  senile  change  this  is  occasion- 
ally met  as  spots  isolated  in  the  cartilaginous  nasal  septum  in  cattle, 
in  the  laryngeal  cartilages  of  dogs,  and  quite  uniformly  in  the  costal 
cartilages  of  old  animals.  (These  foci  become  easily  visible  as 
opaque  points  on  drying  the  cartilage.)  With  much  less  frequence 
than  in  man,  calcification  of  the  vessel  walls  is  observed  in  animals 


2l8 


Retrogressive  Processes. 


as  a  rather  rare  occurrence,  transforming  the  intima  of  the  vessel, 
as  the  aorta,  into  a  rough,  scaly  surface,  or  appearing  as  flat  plaque- 
like or  disc-like  areas,  making  the  vessel  at  such  places  rigid  and 
inelastic.  The  greatest  tendency  to  this  change  is  found  in  the 
large  verminous  aneurisms  in  horses,  which  form  brittle,  hard 
enlargements  of  the  arteries.  The  intima  and  the  media  in  these 
lesions  are  the  especial  seat  of  the  calcification,  preceded  by  hyaline 
degeneration. 


Fig.    33. 

Portion   of    liver    of   a    liorse   with    calcification   of   necrotic    parasitic    foci 

Trolldenier.) 


(After 


In  greater  measure  newly-formed  inflammatory  connective  tissue 
is  rather  often  affected;  thus  the  cicatrized  castration  wound  of 
the  abdominal  wall  in  hogs  may  be  observed  changed  into  a  calcified 
plate  as  broad  as  a  hand,  and  the  opening  into  a  hernial  sac  in  um- 
bilical hernias  in  the  same  animals  is  sometimes  changed  into  a  cal- 
cified ring  of  connective  tissue.  Calcareous  plates  in  the  connective 
tissue  of  the  cow's  udder  are  sometimes  found ;  and  even  the  con- 
nective tissue  of  the  lungs  is  in  rare  instances    (in  cattle)   trans- 


Calcification.  219 

formed  into  a  branched,  rigid  and  corset-like  enclosing  structure. 
In  the  dense  membranes  of  the  spinal  cord,  in  dogs,  calcareous  in- 
filtration gives  rise  to  rigid  thickenings  which  feel  like  splinters 
of  wood.  Bursce  and  tendon  sheaths  in  horses  may  become  ex- 
tensively calcified  and  ossified.  The  colloid  matter  often  met  in  the 
thyroid  gland  and  sometimes  involving  the  connective  tissue  as  well 
as  the  acini,  may  occasionally  terminate  in  calcification  of  the  organ 
(stoa.e  goitre,  slniDia  pctrifica}is,m  dogs).  The  herbivora  and  also 
hogs  are  with  special  freciuence  subject  to  calcareous  infiltration  of 
tuberculous  caseated  tissues.  The  yellow,  cheesy  foci  produced 
by  coagulation  necrosis  are  frequently  full  of  sandy,  gritty  particles 
and  are  very  hard.  In  the  end  dead  parasites  and  the  connective 
tissue  capsules  which  are  formed  about  such  foreign  bodies  in  the 
parenchymatous  organs,  as  echinococci  and  round  worms  in  the 
livers  of  horses,  become  so  permeated  with  lime  salts  that  they  form 
stony,  bone-like  or  mortar-like,  chalky  masses. 

In  women,  dead  foetuses  long  retained  in  the  uterus  or  peritoneal 
cavity  may  become  so  completely  calcified  as  to  be  of  stone-like  hardness 
{petrified  foetus,  lithopcrdion)  ;  in  our  dom.estic  animals  the  dead  embryos, 
which  are  often  found,  usually  remain  more  or  less  leathery,  pliable  and 
merely  mummified.  [In  the  museum  of  the  Medical  Department  of  the 
University  of  Pennsylvania  there  is  a  thoroughly  calcified  excellent  example 
of  a  lithopa^dion  taken,  after  death,  from  the  uterus  of  a  mare,  and  pre- 
sented to  Dr.  James  of  the  above-named  institution  in  185 1  by  -\Ir.  Kearney 
of   Gloucester   County,   New  Jersey.] 

Zschokke  (Schicci::.  Archil'.  1902)  has  descrilK-d  a  peculiar  crystalline 
deposit  observed  in  the  liver  of  a  cow  confined  to  the  interstitial  spaces 
as  white  foci,  scattered  here  and  there.  The  abundant  precipitate  was 
made  up  of  rounded  and  rhombohedral  crystals  (about  the  size  of  white 
blood  corpuscles),  the  chemical  nature  of  which  was  not  precisely  deter- 
mined, although  with  the  iodine-sulphuric  acid  test  they  showed  some 
relation  to   cholesterin. 

Solid  u.norganized  bodies  which  are  formed  in  the  secretions  and 
cavities  of  the  body  are  called  concretions.  They  are  formed  by 
the  precipitation  of  salts  which  have  become  insoluble ;  their  chemi- 
cal composition  depending  upon  the  ingredients  of  the  normal  se- 
cretions and  its  existing  changes,  and  therefore  not  uniform. 
Sometimes  they  contain  organic  matter  mingled  with  the  saline 
constituents ;  or  they  may  be  foreign  bodies  or  exudates  which  have 
become  encrusted  with  salts.  The  fundamental  conditions  for  the 
formation  of  these  bodies  include  the  following: 

I.  Supersafnnttion  of  the  saline  solution  (Klimmer)  and  dim- 
inution  of  the  medium   of  solution.     Just  as  the  crystalline   salt 


220 


Retrogressive  Processes. 


separates  from  a  saturated  solution  of  copper  sulphate  or  from 
Carlsbad-Sprudel  water,  in  the  same  manner  the  salts  of  a  secre- 
tion, like  the  urine,  may  precipitate,  especially  should  there  occur 
a  loss  of  its  fluid  or  of  substances  which  keep  the  salts  in  solution. 

2.  Retention  of  secretions  or  excretions  in  their  storage  reser- 
voirs. 

3.  Chemical  decomposition  of  the  secretion,  with  the  formation 
of  insoluble  products,  as  may  result  from  the  presence  of  bacteria 
( ammoniacal  fermentation ) . 

4.  Presence  of  a  foreign  body  or  any  organic  material  which 
serves  as  a  nucleus  for  the  deposition  of  crystals,  or  as  a  supporting 

framework  for  the  precipi- 
tated salts,  as  bits  of  wood, 
particles  of  food,  or  viscid 
degenerative   products. 

Urinary  Calculi  {Uro- 
lithiasis s^ravel,  concrc- 
nicnta  urinaria). — The  sa- 
line constituents  of  the 
urine  may  be  precipitated 
in  the  kidneys,  in  the  renal 
pelvis  and  in  the  urinary 
bladder  and  give  rise  to  the 
formation  of  urinary  gravel, 
urinary  sand,  and  larger 
urinary  calculi.  Even  nor- 
mally in  the  horse,  calcium 
carbonate  separates  in  the 
pelves  of  the  kidneys  and 
in  the  bladder  from  the  al- 
kaline urine,  the  latter  being  turbid  even  when  freshly  passed  in 
consequence ;  in  the  other  herbivora  it  becomes  cloudy  soon  after  it 
is  voided  because  of  loss  of  the  solvent  power  of  its  fluid  on  cool- 
ing. The  acid  urine  of  carnivora  and  omnivora  is,  on  the  contrary, 
clear  and  permits  sedimentation  only  after  decomposition  and  long 
standing.  The  causes  of  urinary  calculus  formation  may  include 
such  structural  elements  as  parasites,  blood  clots  and  coagulated 
fibrin,  shreds  of  necrotic  tissue,  tube  casts  and  epithelial  cells,  these 
substances  afifording  a  place  of  attachment  for  deposition  of  the 
inorganic  substances.  The  presence  of  living  or  dead  bacteria  is 
especially  apt  to  cause  precipitation,  these  at  times  forming  small 


Fig.  34. 

T'rinnr.v      falciilus      from      renal      pelvis      of 
horse. 


Concremcnt  Poniiatioii.  ■  221 

masses  and  favoring",  as  do  protein  chimps,  the  adhesion  of  any 
precipitate,  and,  too,  perhaps  causing  ammoniacal  fermentation. 
A  high  proportion  of  sahnes  in  the  nrine  is,  as  pointed  out  hy 
Klininier.  an  important  feature.  This  authority  questions  whether 
the  presence  of  albuminoid  or  mucoid  substances,  such  as  are  occa- 
sioned in  the  urinary  tract  l)y  inflammation,  provides  any  means  of 
cohesion,  as  a  sort  of  paste.  .Some  such  organic  stroma  is  uniformly 
found,  especially  because  the  concretions  determine  a  catarrhal  pro- 
cess at  times,  as  a  result  of  which  layers  of  mucus  and  albuminous 
material  are  found  between  the  mineral  deposits  ;  such  viscid  matter 
is,  however,  also  found  in  loose  sediments  and  perhaps  may  in 
reality  interfere  with  calculus  formation  by  preventing  [approxima- 
tion and]  cohesion  of  the  particles.  Such  organic  framework  is  not, 
as  pointed  out  by  Moritz,  peculiar  to  calculi,  but  is,  too,  an 
important  feature  in  any 
urinary    crystal,    whatever 

it  ma\-  be.     The   size   and  ^■\<^^'v^'^>-<S^-  \ 

shape    of    urinary    concre- 
tions   varies    widely    with  ' /<.■*-'/ -CC^lNV^^^^$^W<0 -" « ,  ^ 
the  species  of  animal,  the 
site  of   formation  and  the 
composition.       Renal     cal-               '''"^i;^^.-? 

culi     are     usually     round,  '^ 

•^  Fig.  35. 

pearl-shaped,    like    writing  y^^.^^^^  calculus  from  a  horse, 

sand,   millet  seed  or  hemp 

seed  :  those  of  the  renal  pelvis  are  irregular,  warty,  or  correspond  to 
the  shape  of  the  pelvic  cavity,  crcscentic,  and  may  reach  a  size  nearly 
that  of  a  fist.  Tn  the  bladder  the  urine  throws  down  a  slimy,  sandy 
material  which  forms  a  thick,  soup-like  urine  or  masses  which 
may  attain  several  pounds  in  weight  and  assume  the  shape  of 
half  of  a  pear  (corresponding  to  the  interior  of  the  bladder  and 
flattened  on  one  side  by  the  passage  of  the  urine).  When  com- 
pact, vesical  calculi  are  lentil  shaped,  oval,  flattened  or  faceted 
from  pressure,  polished  or  sometimes  rough  and  mulberry-like, 
gland  shaped,  and  range  in  size  from  that  of  a  millet  seed  to  the 
size  of  a  double  fist.  Small  concretions  met  with  in  the  ureters  or 
urethra,  and  often  impacted  in  these  passages,  are  not  formed  in 
this  situation,  but  are  swept  from  the  kidneys  or  bladder.  The 
color  of  urinary  calculi  is  usually  brown,  metallic,  bronze-like ; 
some  concretions  are,  however,  gray,  ye^lo^^•ish  or  piu'c  white,  anc| 
occasionally  reddish  ones  are  met. 


222 


Retrogressive  Processes. 


In  construction  and  chemical  composition  of  urinary  calculi  a 
large  variety  of  substances  take  part ;  and  the  concrement  is  rarely 
made  up  of  but  a  single  chemical  constituent,  but  usually  contains 
a  number  of  ingredients.  In  horses  these  calculi  generally  contain 
carbonates  and  phosphates  of  lime,  carbonate  of  magnesia,  traces 
of  iron  and  occasionally  silicates ;  those  of  the  cow,  sheep  and  goat 
are  at  times  rich  in  silicates  or  magnesium  phosphate,  but  also 
contain  calcium  carbonate  or  triple  phosphate.  In  swine  they  are 
made  up  either  of  triple  phosphate  or  calcium  and  magnesium 
carbonate  and  phosphate ;  and  oxylate  concretions  also  occur.  The 
uroliths  of  carnivora  are  a  mixture  of  calcium  carbonate,  phosphate 
and  urate,  or  are  composed  in  other  cases  of  uric  acid  or  sodium 


» 


Fig.    36. 
Eenal   calculi  from   cow. 


and  ammunium  urates  or  of  calcium-ammonio-magnesium-phcs- 
phate.  The  tabular  forms,  when  fresh  of  soft  consistence  and  of 
greasy,  slimy  appearance,  are  mainly  made  up  of  cystin.  The 
color  of  urinary  concretions  is  given  by  the  pigment  of  the  urine 
or  biliary  pigment ;  occasionally  hsematin  has  been  found  to  explain 
the  existence  of  a  black  color,  or  carbonate  of  iron  that  of  a 
metallic  bronze  luster  (Fiirstenberg,  Pflug,  Miiller,  Dammann, 
Klimmer). 

The  especial  causes  of  danger  in  connection  with  urinary  calculi 
are  to  be  found  in  the  disturbances  of  urinary  flow  which  they 
occasion,  giving  rise  perhaps  to  urinary  retention.  In  addition 
these  foreign  bodies  act  as  irritants  to  the  mucous  membranes  in 


Concrement  Formation.  223 

varying  grade;  may  cause  dysuria  (tenesmus)  and  pain  of  intense 
severity  (spasm  of  the  involuntary  musculature  of  the  ureters, 
bladder  and  urethra),  local  inflammation  and  erosion,  obstruction 
of  urine,  dilatation  of  the  bladder  and  possibly  rupture,  hydrone- 
phrosis, and  submucous  urinary  infiltration  and  urinary  intoxica- 
tion of  the  blood.      (For  details  cf.  SpccicUc  pat  hoi  Anatomic  d. 

Hausfior,  II.  Bd.). 

Gall  Stones  (Cholelithiasis).— Although  in  man  gall  stones  are 
comparatively  common  (25  per  cent,  of  women  sufifer  from  them), 
they  are  rather  rare  in  animals.  They  are  found  as  soft  or  half 
solid,  slippery  bodies  in  the  gall  ducts  and  gall  bladder,  about  the 
size  of  a  hazelnut  but  sometimes  even  larger  than  a  fist,  usually 
multiple  in  numbers  and  often  occurring  in  hundreds.  Their  color 
is  either  a  fine  saiTron  or  ochre  yellow,  brick  red  or  dark  brown, 
or  they  are  whitish  and  chalky,  with  a  yellowish  or  a  greenish  color 
on  the  outside  or  in  layers  internally.  The  larger  ones  are  rounded 
or  oval  in  form  and  in  section  they  show  a  laminated  structure ;  or 
thev  are  from  mutual  pressure  faceted  and  polyhedral  because  of 
their  softness. 

Their  composition  varies.  From  analyses  made  by  INIaly,  Phip- 
son,  Hermann,  of  the  gall  stones  of  cattle,  these  concretions  were 
found  peculiarly  rich  in  bilirubin  or  the  compound  of  bilirubin  with 
calcium  (28-61  per  cent.)  and  poor  in  cholesterin  (only  1.35  per 
cent. ;  according  to  Zschokke,  10-15  per  cent.) .  E.  Voit  found  in  a  gall 
stone  of  a  horse  but  little  biliary  pigment,  no  cholesterin,  large 
amounts  of  biliary  acids,  and  in  the  ash  chiefly  calcium  phosphate. 
In  the  large  examples  not  infrequently  food  particles  (bits  of  cereals 
or  of  hay  or  straw)  are  present,  apparently  forced  from  the  intestine 
into  the  widely  dilated  and  relaxed  biliary  canal  (peristalsis).* 

The  origin  of  gall  stones  is  not  as  yet  entirely  clear.  Accord- 
ing to  Naunyn  the  mucous  membrane  of  the  gall  passages  in 
catarrhal  conditions  produces  a  secretion  rich  in  calcium  salts,  and 
at  the  same  time  albumen  is  exuded  into  the  bile.  The  presence 
of  the  albumen  favors  the  precipitation  of  the  lime,  and  the  increased 
proportion  of  bilirubin  may  be  explained  by  the  thickening  of 
the  bile  from  retardation  of  its  flow.  [The  solid  pigmentary  sub- 
stance in  gall  stones  is  a  definite  chemical  combination  between 
calcium  and  bilirubin,  the  latter  having  feeble  acid  combining 
powers.] 

♦Occasionally  in  swine  and  doer  accnmulations  of  ordinary  sand  (silicate  and 
quartz  fragments)  have  heen  found,  which  could  not  possibly  get  into  the  biliar;r 
passages  except  from  duodenal  contractions. 


224 


Retrogressive  Processes. 


Cholesterin  gall  stones  are  apparently  the  result  of  a  pathological 
secretion  from  the  biliary  mucous  membrane ;  according  to  Gamgee,  in 
cholecystitis  there  may  be  observed  myeline-like  masses  in  the  epithelial 
cells,  a  lump}%  glistening  substance,  which  floats  on  bile  and  which,  on 
the  addition  of  acetic  acid,  crystallizes  as  cholesterin.  These  cholesterin 
clumps  are  regarded  as  the  stage  preceding  the  deposition  of  cholesterin 
for    the    formation    of    calculi     (Naunyn). 


7. 


X 


ww^iml.' 


Fig.   37. 
Gallstones  from   cow.      (After  Trolldenier. ,) 

It  has  been  pointed  otit.  too,  that  colon  bacteria  or  a  mixed 
infection  penetrating  from  the  intestine  may  set  up  a  cholangitis 
and  cause  disintegration  of  the  secretion  and  exudate  and  in  this 
way  give  origin  to  calculus  formation  (Halia,  Naunyn). 

The  presence  of  biliary  concretions  may  produce  no  symptoms  as 
long  as  the  bile  is  able  to  flow  without  interference;  but  at  times 
by  obstructing  the  biliary  passages  they  cause  biliary  stasis  and 
jaundice  or,  by  involvement  of  the  cystic  duct,  retention  of  the 
mucus  in  the  gall  bladder  with  marked  dilatation  of  the  latter 
{hydrops  z-esicce   fellecs).     These   calculi    with   their   b^^cteria   and 


Coitcrcnioit  Poiinatioii. 


225 


particles  of  food  within  llicni  may  excite  inflammatory  changes,  and 
give  origin  to  hihary  colic  from  the  s])asm  and  inllammation  of  the 
muscular  wall  of  the  bladder;  and  it  is  possible  that  rupture  of  the 
latter  may  occur. 

Salivary  Calculi  (calculi  salii'ulcs). — Small  concretions  and  cal- 
culi are   formed  from  the  calcium  salts  of  the  secretion    (calcium 


ry 


Fig.    38. 
Sectioned    surface    of    a    gall    stone    of    a    cow.      (After    Trolldenier. ) 

carbonate  and  phosphate)  and  from  carbonate  of  magnesium,  potas- 
sium and  sodium  in  the  ducts  of  the  oral  salivary  glands  (parotid, 
sublingual  and  submaxillary)  and  of  the  pancreas  (abdominal 
salivary  gland).  These  concretions  are  usually  chalky.  In  the 
horse  salivary  calculi  sometimes  form  in  Steno's  duct  to  the  size 
of  a  goose  egg  (200  to  600  grams  in  weight),  often  having  as  a 
nucleus  a  bit  of  chaff,  a  piece  of  straw  or  an  oat  seed,  which  has 
in  some  way  gotten  in  from  the  mouth.  According  to  Galippe 
bacteria  by  inducing  fermentative  changes  in  the  saliva  seem  to 
be  the  occasion  for  the  separation  of  the  salts. 


226 


Retrogressive  Processes. 


The  larger  calculi  cause  distension  of  the  passages  and  retention 
of  the  secretion.  The  earthy  salts  of  the  saliva  may  also  precipitate 
in  the  mouth  cavity.  Mixed  with  desquamated  epithelium  and 
oral  vegetable  organisms  they  accumulate  as  hard,  brittle,  dirty- 
white  deposits,  particularly  about  the  neck  of  the  teeth,  forming 
the  so-called  tartar  (common  in  dogs,  rare  in  horses). 

Intestinal  Calculi.  Fecal  Concretions. — Indigestible  parts  of 
the  food  and  earthy  substances  with  them  sometimes  accumulate 
in  the  large  intestine  in  more  or  less  compact  masses, 
which    may    have    important   consequences    upon    and    menace   the 


Fig.    39. 

Vegetable  concretion  from   the  colon  of  a  horse. 

health  of  the  animal.  In  the  dog,  more  rarely  in  the  cat,  bone  frag- 
ments in  the  fecal  material,  forming  in  hard,  dirty  brow'n  to  black 
sausage-shaped  masses,  and  perhaps  reaching  the  thickness  of  the 
human  arm,  are  quite  likely  to  block  up  the  rectum  and  colon  and 
cause  erosion  and  necrotic  ulcers  of  the  mucous  membrane,  obstruct- 
ing all  the  rest  of  the  intestinal  contents,  and  producing  fecal 
fistulse  and  rupture  of  the  intestine.  In  horses  concretions  made  up 
of  vegetable  fibres  are  often  formed  in  the  c?ecum  and  colon,  com- 
pressed into  ball-like  clumps,  sometimes  attaining  the  size  of  a 
human  head,  and  more  or  less  encrusted  with  mineral  matter 
(phytoconcrements,  mixed  conerements). 


Concvcuicnt  lu>niiatioii. 


227 


In  the  parts  of  the  large  intestine  just  mentioned  there  are  also 
found  not  infrequently  hard,  stony  concretions  {intestinal  calculi, 
enteroliths),  ranging  in  weight  up  to  eleven  kilograms,  looking 
not  unlike  billiard  balls  or  bowling  balls,  or  sometimes  of  pyramidal 
shape  from  being  worn  off  on  the  sides.  The  main  constituent  of 
these  dense  calculi  is,  according  to  Fiirstenberg  and  Gurlt,  ammonio- 
magnesium  phosphate  (over  ninety  per  cent.),  the  precipitation  of 
which  occurs  especially  in  feeding  wheat  and  rye  bran  (the  horses 
belonging  to  millers  and  bakers),  such  a  food  containing  a  large 
amount  of  magnesium  phosphate.  This  is  dissolved  in  the  acid 
intestinal  juice  and  in  case  of  the  development  of  ammoniacal  com- 
pounds unites  with  the  ammonia  to  form  the  almost  insoluble  triple 


Fig.  40. 
Half    of    a    fractured    laiiiellaterl    enterolith    from    a    horse. 

phosphate.  The  marked  sluggishness  of  peristalsis  which  obtains 
with  this  diet,  and  ammoniacal  fermentation  of  the  intestinal  con- 
tents by  bacteria,  aid  in  the  formation  of  the  calculi.  Usually  the 
larger  examples  are  single :  but  of  the  smaller  sizes  there  may  be 
dozens  or  hundreds  in  one  intestine.  In  addition  to  pressure  ero- 
sions caused  in  the  mucous  membrane  by  these  calculi,  they  may 
produce  fatal  results,  especially  by  accidental  impaction  and  ob- 
struction at  some  narrow  part  of  the  intestinal  tube.  (For  details 
cf.  SpczicUe  pathol.  Anatomic  d.  Haiisticrc,  II.  Aufl.  1902,  Stutt- 
gart, Enke's  Verlag.)  Horses  which  take  in  sand  and  mud  in 
drinking  from  pools  (and  the  same  is  true  of  hogs  from  swallowing 
ground  while  rooting)  occasionally  get  large  masses  of  such  ma- 
terial into  the  intestine  and  may  as  a  result  suffer  from  the  forma- 
tion of  diverticula. 


228 


Retrogressive  Processes. 


In  pigs  bristles  which  are  swallowed  may  be  massed  together 
in  the  intestine  by  the  peristaltic  movements  into  cylindrical  bristle 
balls;  in  ruminants  hair  which  has  been  swallowed  may  form  in 
the  abomasum  one  or  more  spherical  felt-like  bunches,  and  in  the 
same  way  remnants  of  plant  fibres  may  also  be  compressed  into 
similar  balls  here  {piUconcrcniciits,  phytoconcrements,  bezoars). 


Fig.   41. 
Cut   surface   of   half   of  an   enterolith   from   horse    (one-half   reduced). 

Pus  concretions  result  from  the  inspissation  of  pus  retained  in 
old  abscesses  and  other  places,  possibly  with  more  or  less  calcifica- 
tion. In  the  air  chambers  of  horses  they  are  met  quite  commonly, 
supposed  to  be  due  to  the  compression  of  thick  streptococcus  pus 
by  muscular  pressure  (movements  of  chewing  and  swallowing), 
often  into  chestnut-like  or  potato-like  masses.  In  cattle  tubercu- 
lous caseated  masses  in  bronchiectatic  cavities  may  form  hard 
lumps,  perhaps  reaching  the  size  of  a  fist. 


Gout. 


229 


Gout. 

This  name  is  applied  to  a  disturbance  of  metabolism  characterized  by 
accumulation  and  deposition  of  urates  of  the  alkalies  in  the  tissues,  the 
joints  being  special  seats  of  uratic  deposits,  and  developing  painful  nodular 
swellings  (gouty  nodes;  tophi,  from  t64)  os,  cretaceous  stone).  In  man 
this  is  a  common  affection,  but  a  rarit}'  among  mammalian  animals. 
Only  one  case  is  on  record  (Bruckmiiller)  in  a  hunting  dog.  (In  two 
published   cases   in   swine    [Virchow,   Mendelsohn]    there   was   not   a   deposi- 


Flg.   42. 
Pus    concretions    from    au    air    ohamljei-    of    house    (reduced    one-half). 


tion  of  urates,  but  it  would  seem  that  the  whitish,  chalky  masses  found 
in  the  joints  were  composed  of  guanin,  or,  according  to  Voit,  of  tyrosin.) 
Genuine  gout,  however,  is  common  in  pigeons,  chickens,  parrots,  ostriches, 
and  is  quite  frequent  in  birds  of  prey  (Kionka)  ;  it  has  been  observed,  too, 
in   reptiles    (alligators,    snakes). 

The  symptoms  of  avian  gout  manifest  themselves  by  progressive  weak- 
ness  of  the   bird,   with   loss   of   appetite   and    emaciation.     The    legs   present 


230  Gout. 

more  or  less  prominent  arthritic  swelling  and  are  unfit  either  for  standing 
or  walking.  Sometimes  there  is  also  a  swelling  of  the  wing  joints,  and 
in  case  of  chickens,  a  strong  bluish-black  discoloration  of  the  comb  becomes 
apparent.  At  autopsy  of  birds  dead  from  the  affection  after  a  course 
of  some  weeks  or  months,  there  is  at  times  found  within  and  about  the 
joints  a  deposit  of  white,  chalky,  mortar-like  material;  and  the  serous 
membranes  (membranes  of  thoracic  and  peritoneal  air  chambers  and  peri- 
cardium), the  epicardium  and  the  liver  are  apt  to  be  found  the  seat  of 
similar  deposits,  as  though  powdered  with  plaster  of  Paris.  The  kidneys 
are  thickly  beset  with  white  points  and  sometimes  the  ureter  is  completely 
filled  with  white  plugs.  Microscopic  examination  shows  the  condition 
.to  consist  of  a  deposit  of  and  infiltration  with  crystals  of  sodium  urate 
(plates   and   needle-shaped   crystals   grouped    in    stellate   bunches). 

As  far  as  the  causative  conditions  and  nature  of  the  metabolic  dis- 
turbances, fundamental  to  the  affection,  are  concerned,  but  little  has  been 
definitely  established  in  case  of  human  beings.  Practically  all  that  is  known 
is  that  certain  kinds  of  food  (large  amounts  of  albuminates,  highly  sea- 
soned meats  [meats  rich  in  nucleo-proteids],  alcohol),  lead-poisoning  and 
a  predisposition  of  the  individual  play  a  part.  It  has  been  established 
in  case  of  avian  gout,  by  the  highly  interesting  investigations  of  Ebstein, 
Kionka  and  Kossa,  that  a  number  of  poisons  which  injure  the  renal 
tissue  and,  too,  exclusive  meat  diet  are  capable  of  inducing  in  experimental 
cases  the  characteristic  features  of  gout.  As  early  as  1766  Galvani  pointed 
out  that  chickens  became  gouty  after  ligature  of  both  ureters,  an  ob- 
servation which  has  been  repeated  by  Zaleski,  Colasanti,  Schroder  and 
others.  Ebstein  injected  subcutaneously  in  chickens  neutral  chromate  of 
potassium  in  separate  doses  of  0.32  gram,  with  the  idea  of  impairing  the 
excretion  of  uric  acid  by  producing  serious  renal  lesions ;  with  this  dosage 
the  birds  lived  for  some  weeks,  and,  as  a  matter  of  fact,  Ebstein  estab- 
lished that  they  undoubtedly  became  gouty.  The  same  results  were  obtained 
by  v.  Kossa  in  chickens  by  intramuscular  injections  of  solutions  of  oxalic 
acid,  phenol,  acetone,  aloin,  corrosive  sublimate  and,  too,  cane  sugar. 
Kionka  drew  attention  to  the  fact  that  carnivorous  birds  are  the  ones 
which  are  especially  subject  to  gout,  and  from  a  series  of  studies  estab- 
lished the  fact  that  chickens  on  exclusive  meat  diet  (160  grams  a  day), 
to  which  they  may  become  accustomed,  may  become  gouty  in  the  course 
of  a  few  weeks  or  several  months  and  then  die  of  the  affection.  The 
large,  heavy  breeds  showed  greater  tendency  in  this  direction  than  the 
commoner  small  chickens.  There  were  noted  a  great  increase  in  the 
production  of  uric  acid  with  this  diet  and  a  correspondingly  high  dis- 
charge of  uric  acid  (8-9.5  grams  each  day)  and  of  nitrogen  (3-4-5  grams 
a  day)  in  the  excreta.  Since  M.  Kochmann  has  shown  that  in  dogs,  also, 
when  fed  exclusively  with  horse  flesh,  the  renal  and  hepatic  parenchyma 
suffers  a  change  (parenchymatous  nephritis  and  hepatitis),  and  the  poisons 
above  mentioned  give  similar  results,  v.  Kossa  looks  upon  the  nephritis 
as  the  cause  of  the  toxic  gout  interfering  with  the  elimination  of  urates 
just  as  if  the  ureters  were  ligated.  Under  natural  conditions  almost  every 
chronic  nephritis  in  birds  may  be  followed  by  gout.  Ziirn  once  observed 
the    affection     after     feeding    ustUago     maidis    to     chickens.     The     common 


Gout.  231 

occurrence  of  the  disease  in  birds  of  prey  kept  in  captivity  and  having 
insufficient  exercise,  favors  the  view  that  muscular  activity  lowers  the 
disposition,  or,  in  other  words,  uric  acid  is  destroyed  in  the  working 
muscles.  The  difference,  not  merely  in  diet,  but  in  the  possibility  of 
destruction  of  uric  acid  in  the  muscles,  liver,  kidneys  and  spleen  are 
probably  reasons  for  the  rare  occurrence  of  gout  in  mammals  and  the 
fact    that    it    is    never    seen    in    herbivora. 

[In  man  the  affection,  characterized  not  only  by  the  joint  changes,  but 
also  by  widespread  sclerotic  lesions,  especially  of  the  arterial  system,  is 
referred  to  uric  acid  and  certain  precursors  of  this  substance,  the  purin 
bodies.  These  are  particularly  the  products  of  metabolism  of  nucleo- 
albumens,  and  much'  importance  is  ascribed  to  diet  rich  in  these  albumi- 
nates, young  meats,'  pancreas,  liver,  etc.  Other  factors,  as  insufficient 
exercise,  etc.,  are  also  deemed  important.] 


PROCESSES  OF  REPAIR  AND  NEW  FORMATION 

Regeneration. 

By  the  term  regeneration  is  meant  a  process' of  new  formation 
of  tissue  which  occurs  in  connection  with  tissue  loss,  replacing  such 
loss  and  then  ceasing. 

Renewal  by  metabolism  of  the  functional  capability  of  cells 
remaining  alive  after  fatigue  and  exhausting  diseases  is  known  as 
recovery  or  rccoiisfitiifioii.  In  the  living  organism  cellular  material 
is  being  continually  used  up  and  in  consequence  there  are  always 
some  cells  being  destroyed  and  new  ones  growing  to  take  their  place. 
The  cellular  covering  of  those  surfaces  which  are  in  relation  with 
the  external  world  and  from  which  the  cells  are  loosened  by 
mechanical  influences  (epithelium  of  the  skin  and  mucous  mem- 
branes), is  especially  subject  to  continual  losses  and  compensation 
for  such  losses  by  a  succession  of  new  cells.  In  the  glands,  too, 
there  is  apparently  a  continual  change  of  old  and  new  cells,  as  the 
function  of  the  gland  cells  cannot  but  occasion  in  them  aging  and 
death ;  this  exchange  is  an  active  one  in  the  tissues  of  the  testicles 
during  the  period  of  seminal  production,  and  in  the  ovary,  too,  the 
formation  of  ova  is  in  a  measure  a  regenerative  production.  In 
some  glands  which  form  their  secretions  without  particular  destruc- 
tion of  their  cells  (mammary  glands,  kidneys,  sweat  glands), 
renewal  in  this  sense  is,  however,  not  recognizable ;  and  in  case 
of  the  important  elements  of  the  central  nervous  system,  the 
ganglionic  cells,  it  is  a  question  whether  they  are  at  all  subject  to 
change  or  persist  throughout  the  whole  life  of  the  individual. 

The  cellular  constituents  of  the  blood  and  lymph  are  very  perish- 
able, and  in  the  spleen,  bone  marrow  and  lymph  nodes  compensatory 
production  of  these  corpuscles  is  unceasingly  going  on. 

A  regenerative  process  may  be  regarded  as  pathological  only 
in  the  sense  that  it  occurs  in  connection  with  unusual  losses  of 
substance  or  pathological  lesions  of  tissues,  as  after  ruptures  in 
continuity ;  it  is  in  reality  only  an  exacerbation  of  physiological 
histogenesis  as  the  processes  of  growth  in  both  are  identical. 


Reasons  for  Regeneration.  233 

The  causes,  or  better,  the  reasons  why,  after  tissue  injuries  and 
losses,  regenerative  growth  occurs,  are  complex.  Normal  increase 
of  cells  depends  upon  inherent  peculiarities  of  the  cells  themselves. 
The  capacity  for  multiplication  is  characteristic  of  all  cells  for  a 
certain  time  after  they  are  formed;  it  is  most  active  during  em- 
bryonic life  and  in  youth,  diminishing  and,  within  certain  limits, 
ceasing  after  the  full  development  of  the  body,  as  determined  by 
the  relative  tension  of  the  tissues  and  the  inherited  characteristics 
(phylogenetic).  From  those  influences  exerted  by  the  tissues  upon 
each  other  and  by  which  mutual  restraint  is  maintained  so  that 
an  overgrowth  of  one  cannot  take  place  at  the  expense  of  the  rest, 
the  normal  inter-resistance  of  tissues,  the  so-called  tissue  tension,'^'- 
takes  its  significance.  (However,  as  ^larchand  has  suggested, 
mechanical  resistance  to  growth  does  not  alone  explain  tissue 
equilibrium  ;  there  are  other  participating  influences,  as  nutrition. 
The  constancy  of  the  shape  and  size  of  the  organs  and  the  cells  is 
a  fundamental  peculiarity  of  the  species.) 

\\'e  mav   see   in  many   cases  where   removal   of   normal  tissue 
resistance  has  taken  place   (where,  for  example,  the  tissue  tension 
has  been  released  by  the  formation  of  cavities)  the  parts  bordering 
on  such  situations  assume  active  growth.     This  is  very  strikingly 
apparent  where  there  is  a  cleft  in  the  diaphragm  next  to  the  liver, 
as  the  result  of  which  the  liver  tissue  invariably  grows  through  the 
round  or  oval  diaphragmatic  opening  into  the  chest  cavity    (as  a 
button  goes  through  a  buttonhole),  the  otherwise  uniform  opposi- 
tion which  the  diaphragm  exerts  upon  the  anterior  surface  of  the 
liver  being  interrupted   at  this   position   and  lost.     In   any   defect 
produced  by  trauma  or  analogous  loss  of  continuity  of  the  tissues 
the  normal  resistance  is  more  or  less  lowered  and  the  adjacent  cells 
are  able  to  penetrate   into  the  vacant   space  and  fill   it    (vacuum 
growth).     As  a  result  of  the  displacement  of  the  cells  thus  pene- 
trating the  vacant  area  from  their  original  station,  space  is  afforded 
in  the  latter  position  as  well,  thus  giving  opportunity  for  further 
proliferation  of  the  elements  persisting  there  (Ribbert).     According 
to  Ribbert  the  displacement  of  cells   even   from   distant  positions 
may  be  explained  by  such  a  release  of  tension ;  thus  in  the  regenera- 
tion of  blood,  leucocytes  pass  into  the  circulation  and  spaces  are 
left  in  the  bone  marrow,  which  are  filled  by  newly  forming  cells. 
and   with   the  passage   of   these   the   process   repeats   itself   indefi- 

*  Ribbert  means  by  tissue  tension  not  only  pj-essure   conditions,   but  all  the 
opposing  influences  of  the  various  tissues  upon  each  other. 


234  Regeneration. 

nitely.  Anything,  even  hypersemia,  which  tends  to  separate  the 
tissues,  has  in  Ribbert's  opinion  the  same  effect  to  decrease  tension 
and  produce  space.  Although  objection  may  be  made  that  the  dis- 
tending cause  must  also  have  a  pressure  effect  which  should  inter- 
fere with  growth,  it  must  be  granted  that  the  vessels  distended 
and  engorged  in  hypersemic  conditions  separate  from  each  other 
the  closely  packed  cells,  and  that  similarly  the  filling  up  of  the 
lymph  spaces  with  exuded  material  forces  the  cells  apart  and  in 
this  sense  has  an  influence  to  relieve  tension.  The  release  of 
mechanical  tension  is,  however,  not  invariably  the  only  cause  of 
tissue  growth ;  there  are  other  factors  which  are  operative  to  di- 
rectly stimulate  cellular  proliferation.  There  can  be  no  doubt  that 
increase  of  nutrition,  provided  the  cells  are  in  condition  to 
assimilate  it,  must  necessarily  favor  multiplication.  Especially  in 
inflammatory  regeneration  it  may  be  appreciated  that  there  is  such 
a  rich  nutritive  supply  possible  for  the  cells  at  the  periphery  of 
the  inflammatory  focus  from  the  albuminous  fluid  exudates,  fibrin 
and  products  of  disintegration  of  leucocytes  and  blood  coagula. 
that  there  cannot  but  coexist  a  condition  of  extra  nutrition  of 
these  elements  along  with  relaxation  of  and  space  formation  in 
the  tissue.  The  multiplication  of  tissue  in  chronic  inflammations, 
protracted  hyperemias  and  lym])li  congestions  may  also  be  partly 
explained  by  this  idea. 

In  addition  it  is  possible  that  the  elevation  of  temperature 
attending  inflammatory  processes  may  play  a  part,  as  it 
is  well  known  that  warmth  is  an  important  stimulus  to  cellular 
activity  and  therefore  to  cellulai"  proliferation.  Chemical  agents 
should  also  be  included  among  the  important  factors  of  stimulation 
of  cell  multiplication.  Just  as  the  mobile  leucocytes  are  attracted 
by  nutritive  substances  and  other  materials  and  assume  a  phagocytic 
activity,  the  fixed  cells  respond  to  the  chemotactic  stimulus  of 
nutrient  matter.  They  do  not  merely  manifest  evidence  of  phago- 
cytic action  which  underlies  their  hypernutrition  and  consequent 
cell  division,  but  there  may  be  distinctly  recognized,  as  in  the 
regeneration  of  nerves,  that  there  exists  some  special  substance 
exerting  attraction,  which  determines  the  direction  of  growth  of 
the  proliferating  cells.  Fibrin  especially  seems  to  exert  this  two- 
fold influence  ;  in  most  cases  where  a  layer  of  fibrin  overlies  the 
tissue,  the  latter  is  apt  to  soon  proliferate  into  the  fibrin 
(Marchand).  The  substances  set  free  by  the  destruction  of  leu- 
cocytes   are    apparently   capable    of    exerting   a    chemical    stimulus 


Reasons  for  Rci^^ciicratioii.  235 

in  this  sense.  According  to  ]\larchand  many  cells  have  a  tendency 
to  adhere  to  their  support  with  as  broad  a  base  as  possible  until 
forced  off  by  other  cells  of  the  same  type,  as  may  be  seen  in  the 
wav  young  connective  tissue  cells  force  their  way  into  the  smallest 
cellulose  meshes  of  elder  pith,  necessarily  passing  through  its  nar- 
row pores  and  changing  their  shape  to  marked  degrees.  This  tactile 
stimulus  perhaps  explains  the  tendency  of  connective  tissue  cor- 
puscles to  apply  themselves  about  foreign  bodies,  fibrin  fibrils  and 
analogous  objects. 

In  most  cases  the  causes  enumerated  are  combined  to  give  origin 
to  the  stimulus  for  cellular  proliferation ;  for  example,  where  granu- 
lation tissue  grows  up  and  out  of  a  wound  in  a  luxurious  manner 
instead  of  ceasing  to  grow  after  filling  the  wound  and  then 
cicatrizing,  the  condition  may  be  ascribed  to  the  combined  influence 
of  a  number  of  the  conditions  above  indicated,  as  the  absence  of 
pressure  opposition,  excess  of  nutrition  and  the  action  of  special 
irritants  (saliva,  medicaments). 

Regenerative  capacity  is  possessed  by  the  cells  and  tissues  of 
animals  in  varying  degree.  In  in,vertebrates  and  the  lower  verte- 
brates the  power  of  replacement  or  regeneration  of  important  parts 
after  loss  is  common  to  all  the  tissues.  Both  pieces  of  a  divided 
earthworm  grow  into  perfect  creatures ;  salamanders  and  lizards 
can  reproduce  completely  the  loss  of  a  tail,  with  bones,  muscles,  and 
even  the  portion  of  spinal  cord  belonging  thereto ;  salamanders  can 
form  a  new  leg  in  place  of  one  cut  oft",  or  an  inferior  maxilla 
(Samuel,  Ribbert).  This  extensive  regenerative  capacity  has  been 
tentatively  explained  by  the  supposition  that  such  low  forms  of 
animals  are  more  commonly  subjected  to  injuries  of  the  type  indi- 
cated and  so  their  cells,  naturally  and  because  of  their,  less  com- 
plicated structure,  retain  their  power  of  adaptation  better  than  those 
of  the  higher  animals.  In  the  latter  the  cellular  construction  is 
more  complicated  and  more  fully  developed  for  special  functional 
requirements,  and  possess  a  less  marked  tendency  to  divide  in 
comparison  with  the  simple  cell  forms,  are  less  independent,  and  in 
some  degree  require  the  co-operation  of  other  cells  in  their  nutritive 
processes.  The  more  a  type  of  tissue  or  cell  departs  from  its 
embryonic  state  and  the  higher  differentiation  it  attains,  the  more 
difficulty  it  experiences  in  attempting  regeneration.  The  epithelium 
of  the  skin  and  mucous  membranes  and  connective  tissue  retain 
their  power  of  adjustment  in  response  to  the  numerous  faults  to 
which  they  are  liable,  and  easily  and  quickly  regenerate  in  the 
higher   as   well   as   the   lower    forms    of   life ;    but    the    ganglionic 


236  Regeneration. 

nervous  cells  and  striated  muscle,  which  can  only  exist,  from  a 
functional  standpoint,  in  connection  with  nerves  and  which  are  of 
a  decidedly  complex  structure,  and  in  the  same  way  glandular  cells, 
regenerate  only  under  special  circumstances  or  not  at  all. 

[The  conditions,  then,  which  underlie  cellular  regeneration  may 
be  summarized  somewhat  as  follows:     Only  cells  which  from  the 
simplicity  of  their  structure  and  function  or  from  the  fact  that  they 
have  not  advanced  far  from  their  embryonic  state  are  likely  to  mul- 
tiply with  any  comparative  ease.     Any  cell  must  be  provided  with 
sufficient  nutrition  to  maintain  its  cellular  activity  and  life  if  it  be 
expected  to  divide,  and  extra  nutrition  as  met  in  hypersemia  favors 
multiplication.     Cells  capable  of  division  cannot,  however,  prolif- 
erate if  there  be  important  mechanical  or  physiological  opposition 
exerted  by  the  other  cells  and  structures  of  the  body,  and  release 
of  such    mutual    tension   (mechanical,  nervous,  chemical)   must  be 
afforded  before  proliferation  is  possible.     But  in  addition  a  definite 
stimulus  to  division  should  exist.     This  stimulus  may  be  of  chem- 
ical nature,  perhaps  afforded  by  special  chemical  substances  coming 
to  the  part  from  previous  cellular  disintegration  (here  the  brilliant 
results  of  Jacques  Loeb  in  producing  multiplication  and  develop- 
ment of  unfertilized  ova  of  sea-urchins  by  immersion    in    special 
chemical  solutions  are  strongly  corroborative),  electrical  (here,  too, 
the  work  of  Loeb  and  his  associates   is  illuminating),  thermic  or 
mechanical.] 

In  the   adult  organism  of  animals  and  birds  the   somatic  cells 
reproduce  in  their  process  of  division  and  multiplication  only  cells 
of  their  own  type  (omnis  celhila  e  ccUula  cjusdem  generis)  ;  in  other 
words,  a  newly  formed  tissue  is  invariably  the  product  of  tissue  of 
the  same  kind.     It  was  formerly  believed  the  various  types  of  cells 
could  in  their  multiplication  produce  opposite  types  and  that  in  the 
same  way  as  the  various  organs  arise  by  their  differentiation  from 
the  three  embryonic  layers  similar  transformations  of  tissue  could 
take  place  in  the  restoration  of  post  embryonic  defects.     A  certain 
capacity    for   transformation    (metaplasia)    is    possible    in    related 
types    of    cells    and    their    matrix    products.      Thus    the    different 
varieties  of  epithelial  cells  may  be  changed  by  external  influences 
(pressure)  ;  and  within  the  group  of  connective  tissues  transforma- 
tions occur,  as  the  formation  of  bone  and  cartilage  from  fibrous 
connective   tissue.      But   connective   tissue   is   never   changed    into 
epithelium,   or  the   latter   into   connective  tissue,   the   four   distinct 
groups  of  primary  tissues    (epithelium,  connective  tissue,  nervous 
tissue  and  muscle)    never  interchanging. 


Regeneration  of  Conneetive  Tissue.  237 

The  nature  and  method  of  celhilar  proHfcration,  as  far  as 
nuclear  and  celhilar  division  is  concerned,  is  in  general  the  same  as 
in  normal  life,  although  there  are  pathological  irregularities  met 
in  the  chromatin  network  and  detailed  structure  of  the  protoplasm. 
The  replacement  of  lost  tissue  originates  from  the  cells  which  hap- 
pen to  remain  unchanged  at  the  site  of  the  defect  or  exist  imme- 
diateh-  about  it.  If  there  are  elements  present  in  such  a  position,  of 
the  same  kind  as  those  lost  and  capable  of  multiplication,  their  pro- 
liferation may  completely  restore  the  fault,  the  area  of  loss  being 
filled  up  with  identically  similar  elements  with  the  same  functional 
abilities  (simple  or  eo)iipIefe  re^i^-eiierafioii) .  Should  the  proper 
cells  be  absent  from  the  vicinity  of  the  faulty  area  regeneration 
will  be  incomplete  (false),  and  the  space  will  be  occupied  by  cica- 
tricial tissue  derived  from  the  connective  tissue  structures  every- 
where present. 

Kegeneration  of  Connective  Tissue  and  Bloodvessels.     The  con- 
nective  tissue   framework   is   the   tissue   which   takes   the   principal 
part  in  repair  in  lesions  of  any  kind,  whether  traumatic  lesions  of 
continuity  or  necrobiotic  destruction  of  the  parenchyma  of  organs ; 
usuallv  the   first  elements  to   multiply  being  the   connective  tissue 
cells,  these  taking  the  place  of  the  various  elements  incapable  of 
regeneration.     For  this  purpose  their  power  of  movement  and  of 
taking  up  otlier  cells    and    all    sorts    of    disintegration    products 
makes    them    of    value     to     the     organism     in     the     removal     of 
substance    which    has    become    useless,    and    in    the    construction 
of     a     protective     wall     about      foreign     bodies.      The     greater 
part  of  the  connective  tissue  seen  in  sections  is  made  up  of  minute 
narrow  spindle  cells,  almost  completely  occupied  by  dark  elongated 
nuclei,   and    intervening  bundles   of   fibrils.      In   case   of   prolifera- 
tion   of    this    tissue    these    spindle    shaped    elements    multiply,    the 
nuclei  undergoing  mitotic   division  and   the  protoplasm   increasing 
in   volume.      The   newly   formed    connective   tissue   corpuscles    are 
thicker  and  polymorphous,  sometimes  rounded  or  polyhedral,  and 
provided  with  a  number  of  processes;  they  usually  lie  closely  sit- 
uated,   often   in    rows    one    after    another,    and   show    their   active 
part    in    the    proliferation    b\-    the    presence    of    mitotic    nuclear 
figures    (one  cell  sometimes  contain'ng  two  or  three  nuclei).     As 
they  approach  the  type  of  embryonic  mesoblastic  cells  and  repre- 
sent  the   young   germinal   elements   of   connective    tissue   they   are 
known    (Lebert)   as  fibroplasts     (irXdacHv.     to  form),  or  Hhrohlasts 
(^Xa'TTdvw.      to  germinate).      In   connection   with   the   multiplication 
of  these  cells  there  also  occurs  a  new  formation  of  the  connective. 


238 


Regeneration. 


tissue  fibrils,  the  processes  of  the  fibroblasts  splitting  up  into  fine 
threads,  at  first  in  a  brush  like  fashion,  the  protoplasm  of  the 
cell  gradually  changing  completely  into  a  bundle  of  parallel  fibrils 
(Diirk,  Neumann,  Ziegler).  Thus  by  the  splitting  of  the  enlarged 
cell-body  into  fibrils  the  cell  comes  to  resume  the  type  of  the  fixed 
connective  tissue  corpuscles,  and  the  mass  of  proliferated  fibroplastic 
tissue  assumes  the  character  of  adult  connective  tissue  structure. 
In  addition  to  the  fibrils  the  protoplasm  of  the  connective  tissue 
cells  gives  ofif  a  greater  or  less  amount  of  a  soft  mucoid  inter- 
cellular  substance    (Marchand).     The  young  fibroblasts   are   con- 


^ 


■■H- 


** 


Fig.    43. 
Fibroblasts    and    augiopla.sts    in    granulation    tissue    of   licrse. 

tractile  and  consequently  are  inconstant  in  form  ;  they  can  project 
processes  of  their  substance  and  thus  can  surround  other  cells, 
shreds  of  tissues  and  nutrient  substances  and  incorporate  them 
like  phagocytes.  They  can  also  change  tlieir  position^  this  property 
explaining  the  fact  already  mentioned  that  foci  of  disintegration, 
areas  of  h senior rli,age  and  situations  of  other  types  of  lesions  are 
penetrated  and  occupied,  and  foreign  bodies  are  encapsulated  by 
these  elements.     Their  motile  power  is  so  marked  that  if.  for  ex- 


Regeitcrafio/i  of  Coiinccfk'c  7'issiic.  239 

ample,  a  bit  of  sponge  or  fragment  of  elder  ])ith  be  introduced  into 
a  tissue  or  serous  cavity  it  becomes  completely  penetrated  by  these 
fibroblasts. 

Along  with  the  connective  tissue  cells  proper,  the  endothelial 
cells  of  the  blood  and  lymphatic  vessels  take  part  in  the  new  forma- 
tion of  connective  tissue.  In  both  forms  of  cells  mitosis  prevails 
profusely  ;  the  young  endothelial  elements  resulting  from  the  cell  di- 
vision are  like  the  other  fibroblasts,  being  distinguishable  from  those 
derived  from  the  spindle  cells  only  at  their  places  of  origin  from  the 
blood  vessels,  where  they  are  forming  capillary  tubes.  Whether 
endothelial  cells  ever  form  fibrils  or  solely  develop  into  vessels  is 
not  fully  determined  (for  details  consult  ]\Iarchand).  Another 
long  debated  question,  whether  the  leucocytes  actually  take  part  in 
the  connective  tissue  formation  and  are  transformed  into  connec- 
tive tissue  cells,  may  be  answered  on  the  basis  of  more  recent 
studies  (Marchand)  that  the  white  corpuscles  which  exude  from 
the  blood  vessels  are  principally  concerned  in  the  removal  of  for- 
eign matter  and  products  of  disintegration,  that  they  furnish  nutri- 
tive substance  in  case  of  their  own  destruction,  but  are  incapable 
of  forming  intercellular  material  and  therefore  cannot  be  consid- 
ered as  actual  constructive  elements  of  the  connective  tissue.  The 
presence  of  these  leucocytes  in  every  area  of  proliferating  connec- 
tive tissue  is  therefore  dependent  upon  their  entrance  partly  from 
the  vessels,  partly  from  points  of  lymphoid  development  to  be 
found  commonly  along  the  bloodvessels  in  any  tissue.  The  whole 
cellular  group  more  or  less  closely  approaching  leucocytes  and  cells 
from  the  lymph  glands  (lymphocytes),  but  because  of  their  more 
conspicuous  cytoplasm  or  a  variety  of  granulations  of  their  proto- 
plasm given  other  names  (plasma  cells,  iiiasf  cells,  leucocytoid  cells, 
polyhlasts,  klasinafocytes) ,  are  also  found  in  the  growing  connective 
tissue.  The  origin  of  these  cells  and  tlie  question  of  their  relationship 
is  still  rather  uncertain ;  probably  they  are  all  immigrants  originating 
from  lymphocyte  depots.  Giant  cells  (polykaryocytes)  are  also  often 
observed  in  developing  connective  tissue,  and  multinucleated  cells, 
especially  when  foreign  bodies  are  present ;  they  are  formed  partly 
from  the  multiplying  spindle  cells,  partly  from  endothelial  cells,  and 
may  be  regarded  as  cells  whose  protoplasm  has  increased  and  whose 
nuclei  have  multiplied  more  rapidly  than  cell  division  could  keep  pace 
(proliferation  giant  cells).  According  to  another  view  they  are 
caused  by  coalescence  of  closely  grouped  embryonic  cells  (congluti- 
nation giant  cells). 

Opinions  concerning  the  mode  of  origin  of  elastic  fibres  in  the  re- 


240 


Regeneration. 


generation  of  connective  tissue  are  not  fully  formulated ;  their  forma- 
tion is,  however,  a  slow  process.  It  is  only  after  four  or  six  weeks 
or  after  several  months  after  repair  by  the  fibroplastic  tissue  that 
elastic  fibrils  appear  in  the  intercellular  substance;  and  even  after 
years  these  do  not  attain  the  diameter  of  the  original  elastic  ele- 
ments. 

Connective  tissue,  modified  to  form  adipose  tissue  by  fatty  infiltra- 
tion, is  capable  of  proliferation  to  the  same  extent  as  ordinary  connective 
tissue  cells.  The  nucleated  protoplasmic  remnant  of  the  fat  cell  undergoes 
division,  and  the  new  cells  usually  at  first  accumulate  in  the  fat  vacuole 
within  the  old  cell  membrane. 

Formation  of  blood  z'csscls  takes  place  by  a  process  of  budding 
and  division  of  the  endothelial  cells  from  the  existing  capillaries. 
The  protoplasm  of  the  endothelial  cells  in  the  walls  of  the  old  ca- 
pillaries which  have  remained  intact  send  out  pointed,  conical  proc- 
esses,   which   lengthen   out   in   thread    like    manner,   and   penetrate 


■■-g^S*'*^' 


•;U3^jg^< 


Fig.  44. 

Vascular    sprouts,    highly    magnitied  :     (after    'i'homa).      The    long    thread-like    ends 
of  the  sprouts   are  only   partly  reproduced. 

between  the  proliferating  fibroblasts.  Coincidently  mitosis  of  these 
endothelial  cells  takes  place  and  at  the  base  of  the  bud  cellular 
division  begins  and  the  endothelial  cells  (angioplasts)  proliferate. 
These  new  elements  lie  alongside  of  each  other  and  fuse,  with  their 
often  curved  and  reticular  branches,  into  solid  cords  of  cells. 
From  these  the  capillary  tubes  are  produced  by  the  forcible  pene- 
tration of  the  blood  from  the  old  vessel  in  between  the  dividing 
endothelial  elements,  thus  making  a  space  filled  with  blood.  This 
proceeding  at  all  places  where  these  buds  are  forming,  gradually 
the  whole  network  becomes  canalized.  From  some  of  the  capillaries 
arteries   are  formed,   from   others   veins,   the  lumen  of  the  tubes 


Formation  of  Blood  Vessels.  241 

being  widened  by  blood  pressure  and  growth  of  the  wall  (increase 
of  surface  by  multiplication  of  the  parietal  endothelial  cells)  ; 
smooth  muscle  grow-ing  from  the  existing  arteries  into  the  newly 
formed  vessels,  and  the  surrounding  fibroplastic  tissue  aiding  in  the 
formation  of  elastic  fibres.  (Regeneration  of  blood  vessels  has 
been  especially  studied  by  J.  Arnold,  Jos.  ]\Ieyer,  Billroth,  C.  Weil 
and  Thoma.) 

The  development  of  angio-fibroplastic  tissue  is  accompanied  by 
more  or  less  manifest  phenomena  of  inflammation  (hyperemia, 
exudation  of  leucocytes)  and  is  therefore  in  a  sense  a  result  of  pro- 
ductive inflammation.  Depending  upon  the  number  of  blood  ves- 
sels present  and  the  relative  amount  of  proliferated  connective  tissue 
the  new  structure  presents  a  reddish-gray,  grayish-white  or  pure 
white,  swollen  appearance,  semitransparent  and  of  a  shape  conform- 
ing to  that  of  the  lesion  which  it  has  followed.  \Mien  it  develops 
diffusely,  as  in  parenchymatous  organs,  to  replace  destroyed  gland- 
ular tissue,  it  gives  rise  to  more  or  less  marked  induration  of  the 
part  (indurative  inflammation),  or  forms  translucent  hard  thicken- 
ings (in  fasciae,  serous  membranes),  bands  of  adhesion  (adhesive 
inflammation)  and  sometimes  villus-like  fringes.  In  focal  devel- 
opment it  forms  white  trabecular  or  nodular  connective  tissue 
masses  (in  infarcts  of  the  kidney)  ;  as  the  result  of  a  demarcating 
inflammation  about  some  blood  clot  or  foreign  body  it  constitutes 
a  connective  tissue  capsule.  On  the  free  surfaces  of  wounds  the 
new  formation  is  seen  as  a  finely  granular  soft  tissue,  producing  an 
exudate,  with  a  deep  red  or  reddish  gray  color  from  the  abundance 
of  capillary  buds  in  its  structure :  it  is  known  as  gramilation-tissue. 

All  fibro-angioplastic  tissue  is  at  first  likely  to  form  a  greater 
bulk  than  the  lesion  which  it  replaces.  There  exists  an  excessive 
production  of  the  young  cells  and  these  cause  an  excess  of  inter- 
cellular material.  \\'ith  restoration  of  normal  tissue  tension  and 
maturation  of  the  growing  tissue,  these  originally  enlarged  cells 
shrink  and  the  intercellular  substance  decreases ;  the  fibrils  are  ar- 
ranged in  a  parallel  fashion  from  the  tension  and  pressure  of  the 
neighboring  structures  influencing  them;  some  of  the  capillaries 
become  obliterated,  that  is,  narrowed,  from  pressure  by  the  shrink- 
ing fibroplastic  tissue.  In  this  way,  too,  the  whole  tissue,  some- 
times, because  elastic  tissue  is  produced  in  deficient  amount  or  not 
at  all,  becomes  dense  and  hard  and  is  changed  into  cicatricial  tissue. 
This  is  apt  to  contract  still  further,  thus  forming  in  the  surface  of 
the  skin  and  organs  depressions  or  indentations  of  radiating  stellate 
form. 


242  Regeneration. 

Regeneration  of  Epiderm  and  Epithelium  of  Mucous  Mem- 
branes.— The  epithelium  on  the  surface  of  the  skin  and  mucous 
membranes  is  capable  of  very  rapid  and  complete  regeneration. 
Because  of  the  continual  loss  of  cells  from  desquamation  as  they 
grow  old  the  tissue  is  always  prepared  for  and  actively  engaged  in 
regeneration.  Either  because  of  cellular  tactile  irritability  (v.  p. 
235)  or  because  the  removal  of  tissue  resistance  in  defects  mechan- 
ically causes  it  to  undergo  a  regressive  development,  the  new  tissue 
is  very  apt  to  spread  out  upon  the  free  surfaces  and  to  some  extent 
to  increase  in  volume,  a  flat  cell  thus  arising  from  a  cylindrical  cell 
at  the  border  of  the  lesion.  The  new  cells  are  always  formed  from 
existing  epithelium  and  can  only  be  produced  providing  vitally 
capable  cells  of  the  same  tissue  are  present  in  the  vicinity  of  the 
lesion. 

The  formerly  accepted  belief  that  epithelial  cells  could  develop  from 
connective  tissue  has  been  shown  to  be  erroneous. 

In  case  of  superficial  loss  of  epithelium  (abrasions,  epithelial  ne- 
croses) the  new  surface  cells  grow  over  the  denuded  papilhe  from 
the  margin  of  the  surrounding  epiderm.  Within  three-quarters 
of  an  hour  after  a  wound  has  been  inflicted,  under  the  microscope 
there  may  be  observed  enlargement  of  nuclei  and  direct  and  indi- 
rect nuclear  division  in  the  cells  of  the  stratum  ]\Ialpighii,  both  in 
the  margins  of  the  lesion  and  at  some  distance  from  it ;  after  eight 
or  ten  hours  the  epidermal  border  is  visibly  thickened ;  and  small 
lesions  only  a  few  millimeters  in  circumference  may  be  covered  by 
several  lavers  of  epithelium  in  the  course  of  forty-eight  hours. 
The  epithelium  actually  spreads  over  the  surface  of  the  wound, 
either  from  active  motile  power  or  because  the  superficial  cells  are 
dislodged  by  those  growing  back  of  them  in  the  deeper  layers. 
If  the  part  deprived  of  epithelium  is  covered  by  fibrin,  blood  or  pus, 
a  granulating  surface,  the  proliferating  epithelium  at  the  margin 
forces  its  way  beneath  the  coagulated  crust  over  the  cicatrizing 
connective  tissue ;  in  these  cases  the  epithelial  layer  is  often  rid- 
dled with  leucocytes,  and  afterward  in  the  clefts  and  spaces  thus 
produced  new  cells  may  grow,  forming  branched  plugs  made  up  of 
concentrically  laminated,  keratosed,  epidermal  balls  (horny  pearls, 
atypical  epithelial  proliferation  of  Friedlander).  Occasionally  the 
epithelium  may  penetrate  along  fistulous  passages ;  as  in  a  perforating 
dental  alveolar  fistula  (horse)  the  squamous  epithelium  may  grow 
through  the  alveolus  from  the  mouth  into  the  nasal  cavity.* 

*  Penetrative  growth  of  epithelium  at  the  border  of  ulcers  and  fistuljp 
may  determine  a  free  atypical  new  formation  of  this  tissue  and  thus  give 
rise   to    cancer. 


Regeneration  of  Epithclhun  of  Cornea,  Hair,  Hoof.        243 

The  advancing  margin  of  the  epiderm  may  be  seen  as  a  bluish 
white  wavy  zone,  sometimes  with  a  rosy  tint  from  the  hypersemic 
substructures  showing  through.  Sometimes  in  addition  to  the  epi- 
dermal growth  at  the  margins  of  the  lesion,  islands  of  epithelium 
may  be  observed  in  the  midst  of  the  new  surface.  These  may  origi- 
nate from  the  remnants  of  the  ducts  of  sweat  glands  or  hair  folli- 
cles (the  cells  of  which  are  practically  identical  with  those  of  the 
surface)  which  were  left  intact  because  of  the  superficial  extent 
of  tlie  loss  of  substance ;  or  may  arise  from  epithelial  cells  separated 
from  the  border  and  caused  to  adhere  to  the  surface  of  the  wound 
by  the  application  of  a  bandage. 

The  proliferation  of  the  epithelium  does  not  stop  until  the  free 
surface  of  the  lesion  is  completely  covered.  Epithelial  scars  are  for 
a  long  time  devoid  of  pigment  and  in  a  dark  skin  the  cicatrix  is 
conspicuous  because  of  its  whiteness. 

The  corneal  epithelium  is  ver}-  quickly  reformed  after  destruc- 
tion, a  circular  loss  of  three  millimeters  diameter  being  perhaps  re- 
placed in  the  course  of  from  thirty-six  to  forty-eight  hours.  The 
cells  at  the  margin,  moving  in  by  amoeboid  power  and  flattening  out 
to  form  at  first  a  protective  single  celled  layer,  spread  out  over  the 
surface  ;  these  multiply,  showing  mitotic  figures  and  multinuclear 
examples,  and  build  up  the  layers  of  corneal  epithelium ;  the  cells 
assume  a  cuboidal  shape  and  the  lesion  is  completely  repaired.  In 
case  of  wounds  of  deeper  extent  or  those  perforating  the  whole 
thickness  of  the  cornea  and  involving  the  corneal  connective  tissue 
and  Descemet's  membrane,  the  lesion  is  at  first  filled  up  by  fibrin 
(from  tlie  aqueous  humor).  The  rapidly  growing  epithelium  ex- 
tends over  this  and  forces  itself  into  the  depth  of  the  wound  like 
a  plug.  The  connective  tissue  is  formed  subsequently,  and  on  the 
posterior  surface  the  endothelium  of  Descemet's  membrane  regen- 
erates its  single  layer  of  cubical  cells.  A  milk  white  spot  remains 
at  the  site,  the  result  of  cicatricial  production  by  the  newly  formed 
connective  tissue. 

(Regeneration  of  the  cornea  has  been  exhaustively  studied,  especially 
from   an    experimental    standpoint,    in    animals;    for    details    cf.    Marchand.) 

Regeneration  of  hair  can  occur  only  in  case  the  hair  follicles 
or  portions  of  them  remain.  In  all  deep  cutaneous  lesions  the  cica- 
trix is  permanently  smooth  and  devoid  of  hair. 

Regeneration  of  horny  tissue  of  the  hoof.  After  injuries  to  the 
keratous  envelope  or  after  it  has  been  ruptured  from  suppurations 
of  the  corium  the  horny  layer  may  be  regenerated  by  proliferation 


244  Regeneration. 

of  the  keratogenous  cells  over  the  surface  of  the  granulating  papillae 
and  fleshy  laminse  of  the  persisting  cutis  (the  latter  the  seat  of 
compensatory  and  sometimes  regenerative  changes)  and  the  forma- 
tion of  a  new  protective  layer  over  the  denuded  papillary  surface 
(Gutenacker).  The  first  formed  cells  are  pushed  forward  by  suc- 
ceeding new  growth  and  form  keratous  tubules  by  arranging  them- 
selves in  circles  about  the  papillae ;  later  interpapillary  keratous 
substance  is  deposited  in  the  intervals  between  the  tubules  as  a  yel- 
low, perhaps  soft  and  incompletely  keratosed,  and  usually  very 
thick  mass  (cicatricial  keratin).  In  parts  where  there  are  no 
papillae  the  keratogcnous  cells  are  arranged  in  irregular,  superim- 
posed layers.  Operative  denudations  of  the  corium  of  the  hoof 
from  five  to  ten  square  centimeters  in  area  may  be  completely  over- 
grown by  new  horny  substance  in  the  course  of  from  four  to  six 
weeks. 

(For  details  cf.  Lchrb.  d.  Cliinirgic,  by  Frohner,  and /f M/feranfe- 
heiten,  by  Gutenacker.) 

Regeneration,  compensatory  for  losses  of  cylindrieal  epithelium 
upon  mucous  membranes,  proceeds  in  the  same  way  as  the  process 
in  the  epiderm.  The  epithelial  cells  growing  in  from  the  periphery 
over  the  surface  of  the  lesion  at  first  assume  flat,  then  cubical  and 
finally  cylindrical  shapes  and  in  appropriate  cells  it  is  even  possi- 
ble that  the  ciliated  border  will  be  reformed.  The  surface  epithe- 
lium of  a  wound  of  the  gastric  mucous  membrane  of  a  dog  may  be 
completely  reformed  in  from  four  to  ten  days. 

Regeneration  of  Glands. — Epithelium  of  glands  is  very  irregular 
in  its  regenerative  ability.  The  epithelium  of  glands  of  the  mucous 
membranes  corresponds  histologically  with  that  of  the  surface  of 
the  membrane,  as  in  the  intestine  or  uterus ;  and  therefore  in  these 
parts  epithelial  repair  over  cicatrices,  ulcers  and  wounds  may,  be- 
sides merely  covering  the  surface  of  the  lesion,  sometimes  also  ap- 
parently attempt  gland  formation  in  points  of  depression.  The 
epithelial  cells  formed  in  such  cases  grow  from  remnants  of  in- 
volved glandular  structures  or  from  the  uninvolved  adjacent  tissue 
over  the  seat  of  the  lesion.  The  depressions  occur  at  the 
expense  of  the  young  growing  connective  tissue  or  granula- 
tion tissue  which  is  being  developed  at  the  same  time ;  but  the  more 
marked  the  retraction  of  the  scar  the  less  successful  the  glandular 
reformation.  Ponfick,  Gluck  and  v.  Meister  in  their  interesting  ex- 
periments have  pointed  out  in  connection  with  regeneration  of 
the  liver  that  after  operative  removal  of  a  portion  of  the  hepatic 
tissue  from  rabbits,  rats  and  dogs  a  remarkable  regenerative  activity 


Regeneration  of  Glands,  Spleen,  Lymph  Glands.  245 

occurs.  Alter  ablation  of  half  of  the  bulk  of  the  organ  new  liver 
tissue  developed  from  the  remaining-  portion  by  luxuriant  prolif- 
eration of  the  hepatic  cells,  setting  in  as  early  as  the  third  to  the 
fifth  day;  after  an  average  of  from  forty  to  sixty  days  the  part  lost 
was  completely  restored  in  volume  and  weight.  It  is  conceivable 
that  after  other  local  lesions  liver  tissue  may  regenerate,  yet  after 
traumatic  lesions  or  destruction  of  hepatic  parenchyma  by  the  pene- 
tration of  parasites  nothing  but  cicatricial  connective  tissue  is  seen 
at  the  site  of  the  defects,  always  containing  on  microscopic  examina- 
tion decidedly  proliferated  bile  ducts,  but  without  evidence  of 
formation  of  functionally  capable  liver  cells.  This  probably 
is  due  to  the  fact  that  in  the  type  of  defects  under  con- 
sideration the  connective  tissue  framework  has  also  undergone 
pathological  changes,  and  perfect  restoration  of  functionating 
parenchymatous  cells  can  only  be  expected  when  the  connective 
tissue  basic  structures  are  in  normal  condition  (Ribbert).  The 
enormous  enlargement  of  the  liver  sometimes  seen  in  tuberculosis 
and  echinococcus  disease  is  apparently  due  not  merely  to  the 
foreign  elements  and  to  connective  tissue  hypertrophy,  but  may 
possibly  be  dependent  upon  a  vicarious  hypertrophy  or  regeneration 
of  the  hepatic  parenchyma. 

It  is  not  certain  in  case  of  the  kidney  whether  epithelial  cells 
lost  in  consequence  of  inflammations  and  degenerations  of  the  paren- 
chyma can  be  restored  completely.  Lesions  from  infarction,  suppu- 
ration or  trauma  always  heal  by  cicatrization.  There  may,  how- 
ever, take  place  a  compensatory  hypertrophy  of  adjacent  tubules 
and  glomeruli  to  occupy  the  space  caused  by  shrinkage  of  such 
scars,  which  in  a  measure  may  compensate  for  the  lesion. 

The  tissue  of  the  testicles  and  ovaries  has  but  little  regenerative 
power ;  space  caused  by  trauma  and  degeneration  is  always  filled  in 
by  cicatricial  tissue.  On  the  other  hand  the  glandular  epithelium 
of  the  mammary  gland,  thyroid,  salivary  and  lachrymal  glands  is 
capable  of  extensive  proliferation  from  remaining  portions  of  the 
alveolar  tissue,  with  formation  of  new  ducts  and  glandular  acini 
lined  with  secreting  epithelium. 

The  spleen  and  lymph  nodes  although  subject  to  continual 
change  of  their  cellular  constituents  and  capable  of  originating  in 
pathological  conditions  a  marked  excess  of  their  lymphoid  tissue, 
do  not  regenerate  after  traumatic  lesions,  being  invariably  subject 
to  cicatricial  repair. 

Striated  muscle,  when  the  fibres  have  been  partially  destroyed 
by  degeneration  of  their  substance,  is  able  to  regenerate  in  a  certain 


246  Regeneration. 

measure ;  at  least  microscopically  proliferation  of  remnants  of  nu- 
cleated sarcoplasm  may  be  observed,  whole  chains  or  rows  of  new 
nuclei  being  produced  b}-  direct  nuclear  division,  these  in  asso- 
ciation with  proliferation  of  the  sarcoplasm  by  longitudinal  divis- 
ion going  to  form  the  so-called  muscle  cylinders  (\\'aldeyerj  and 
lateral  olT-shoots  known  as  muscle  buds  (Naumannj.  Apparently 
the  sheath  of  the  sarcolemma  develops  from  the  surrounding  con- 
nective tissue,  which  is  also  proliferating;  and  the  developing  sar- 
coplasm takes  on  a  fibrillar  structure.  In  tramnatic  lesions  connec- 
tive tissue  formation  predominates,  the  healing  of  the  wound  usually 
giving  rise  not  to  the  reconstruction  of  the  contractile  elements, 
but  to  the  formation  of  dense  scars. 

Smooth  muscle  even  in  traumatic  lesions  exhibits  active  mitosis, 
and  multiplication  of  the  muscle  of  the  blood  vessel  walls  is  to  be 
observed  in  granulating  tissue  ;  but  in  lesions  of  muscular  tunics, 
as  of  the  stomach,  intestine  or  uterus,  complete  restitutio  ad  inte- 
grum has  never  been  observed,  scar  formation  taking  place  instead. 

Eegeneration  of  tendon  tissue  (studies  of  this  process  being 
often  afiforded  in  the  rather  common  performance  of  tenotomy) 
begins,  according  to  Alarchand,  principally  from  the  loose  cellular 
tissue  between  the  bundles  of  tendon  fibrils.  This  formative  ma- 
terial, composed  principally  of  spindle  cells,  develops  (by  mitosis) 
into  the  cleft  between  the  cut  ends  of  the  tendon,  which  is  filled  up 
with  blood  or  exudate,  and  unites  the  tendon  stumps  as  a  soft  gray- 
ish fibroplastic  mass.  Later  the  fibroblasts  form  a  fibrillar  matrix, 
the  fibrils  arranged  parallel  with  each  other,  and  the  tendon  scar 
gradually  acquires  great  firmness.  According  to  Paget  a  divided 
tendon  of  Achilles  of  a  rabbit  may  be  found  united  as  early  as  from 
three  to  five  days  and  in  ten  days  may  be  of  sufficient  strength  to 
require  a  tensile  force  of  twenty-eight  pounds  to  tear  it  apart. 

Lesions  of  cartilage,  as  that  of  the  air  passages,  the  auricle,  or 
ribs,  are  restored  by  connective  tissue  formation  from  the  perichon- 
drium, the  cells  of  which  give  origin  to  a  fibrillar,  collagenous  sub- 
stance. The  latter  may  become  homogeneous  and  by  a  metaplastic 
process  the  connective  tissue  thickening  be  converted  into  hyaline 
cartilage ;  and  it  is  possible  that  by  an  infiltration  of  calcareous 
salts  ossification  of  the  embryonic  tissue  occupying  the  space  of 
the  lesion  may  ensue.  The  cartilage  itself  takes  no  part  in  the 
process  of  restoration  and  connective  tissue  scar  formation  is  usually 
but  slight. 

New  formation  of  osseous  tissue  after  fractures  and  operative 
lesions   arises   exclusively   from   the   periosteum  and  bone   marrow 


Regeneration  of  Bone.  247 

and  ends  by  complete   restitution  of  tlie  most  dense  osseous  sub- 
stance.    The  special  bone  cells  embedded  in  a  dense  solid  calcified 
matrix  are  unable  to  take  part  in  the  construction  of  new  tissue 
because  they  have  no  space  for  any  activity.     The  osteoblasts  of 
the  periosteum  and  marrow,  the  bone  forming  cells,  are  connective 
tissue  cells  which  possess  the  peculiar  ability  of  giving  origin  to  an 
intercellular  material   with   an  affinity   for   lime   salts   or  of  them- 
selves producing  calcification  of  the  matrix  and  thus  supplying  the 
basic  osseous  material.     They  are,  however,  also  capable  of  produc- 
ing fibrillar  connective  tissue  and  may  act  precisely  as  fibroblasts; 
and   finally   may  become  transformed   into   cartilage   cells,    form   a 
homogeneous    inter-cellular    material    and    remain    in    the    lacunae 
within  the  latter.     In  bone  repair  therefore  there  is  first  noted  a 
fibroplastic  callus  which  becomes  partly  changed  into  cartilage  and 
later  into  calcified  osseous  tissue.     Coincidently  the  blood  vessels  of 
the  bone   proliferate,   complete   analogy  to   the   vascularized   fibro- 
plastic callus  existing  in   the  healing  of  lesions  of  the  soft  parts. 
The  name  callus  is  applied  to  the  whole  of  the  tissue  arising  in  the 
osteogenetic  process,  its  origin  giving  the  basis  for  differentiating 
between  periosteal  and  myelogenous  callus;  tliat  portion  which  de- 
velops between  the  separated  fragments  is  known  as  the  iiitcruicd- 
iate  callus. 

In  the  neighborhood  of  the  seat  of  fracture  all  of  the  periosteal 
and  marrow  cells  and  vascular  endothelial  cells  become  swollen,  nu- 
clear division  actively  proceeds,  and  cellular  proliferation  is  so  lux- 
uriant that  the  capillaries  are  often  found  occluded  by  young  endo- 
thelial cells  and  giving  off  profuse  vascular  buds  ;  the  whole  cellular 
callus  forming  a  growth  decidedly  exceeding  the  diameter  of  the 
bone  itself  (the  widei  tlie  space  between  the  bone  fragments  the 
greater  this  mass). 

This  callus,  at  first  consisting  of  connective  tissue  and  some- 
times called  the  provisional  callus,  has  to  do  with  the  removal  of  the 
clotted  blood  occasioned  by  the  fracture  and  other  tissue  remnants, 
even  of  small  splinters  of  bone  (the  limy  material  of  which  is  dis- 
solved by  the  proliferating  cells),  through  phagocytic  cells  originat- 
ing from  its  newly  forming  constituents.  It  has  a  bacon-like,  cartilag- 
inous appearance,  surrounds  the  ends  of  the  bone  as  a  thick  girdle, 
occupies  the  medullary  cavity  at  the  level  of  the  fracture  and  the 
whole  space  between  the  broken  ends.  The  newly  formed  material 
is  markedly  in  excess,  and  after  calcification  the  osseous  scar  unites 
the  fragments  as  a  clumsy,  thick  enlargement  of  the  shaft  of  more 
or  less  spindle  shape,     ^^'ith  calcification,  which  renders  the  callus 


248  Regeneration. 

hard  like  ivory  and  of  the  compactness  of  cortical  bone,  the  osteo- 
blasts in  the  provisional  callus  are  gradually  enclosed  in  the  calci- 
fying matrix  and  shrink  into  the  spindle-shaped  and  stellate  form  of 
bone  corpuscles ;  the  newly  formed  vessels  with  their  contained  blood 
persist  in  the  calcifying  osteoplastic  tissue,  giving  an  analogy  to 
the  svstem  of  the  Haversian  canals  of  bone.  There  is,  however,  no 
lamellated  structure  in  the  tissue.  After  the  osseous  scar  has  become 
hard  and  the  bone  is  again  strong  enough  to  sustain  weight  and 
muscular  strain,  a  reduction  of  the  excessive  callus  sets  in,  aplana- 
tion  of  the  callus;  the  external  bulging  of  the  bone  diminishes;  the 
periosteum  becomes  closely  adherent;  the  medullary  callus  becomes 
porous,  the  medullary  canal  opens  and  the  medullary  substance  be- 
comes full  of  fat.  These  changes  in  the  callus  are  brought  about 
by  the  growth  of  blood  vessels  into  it  from  the  marrow,  and  by 
the  influence  of  multinucleated  giant  cells  of  the  medulla  known  as 
osteoclasts  ( KXacnye^v ,  to  break)  because  of  their  agency  in  breaking 
down  osseous  tissue  (Rindfleisch ).  The  shrinkage  is  explained  by 
the  biological  law  that  lack  of  use  causes  structures  to  become 
atrophic,  only  functionating  parts  being  maintained.  Hence  in 
conformity  with  this  rule  only  those  portions  of  the  bony  tissue 
which  are  required  to  sustain  weight  or  to  oppose  strain  persist  as 
compact  structures. 

It  is  well  known  tliat  the  texture  of  any  bone  shows  an  arrange- 
ment of  its  osseous  trabecula  conforming  to  the  mechanical  forces 
acting  upon  it;  this  functional  adaptation  is  operative  as  well  as  all 
pathological  conditions  which  occasion  new  mechanical  features.  In 
the  regenerated  bone  tissue  the  resumption  of  function  not  only 
assures  the  maintenance  of  the  osseous  scar,  but  in  addition  de- 
termines the  precise  arrangement  of  its  osseous  trabecula  by  fur- 
ther thickening  of  those  portions  which  are  most  heavily  taxed :  the 
direction  of  the  trabecular  adjustment  develops  in  correspondence 
with  the  lines  of  stress  determined  by  their  functional  relations  in 
supporting  the  body  weight  and  opposing  muscular  strain. 

Regeneration  of  Nerves. — Peripheral  nerves  severed  from  their 
connection  with  the  central  nervous  system  by  section,  contusion 
or  other  destructive  lesion,  degenerate  from  the  point  of  the  lesion 
centrifugally  to  their  peripheral  end  fibres,  their  axis-cylinders  and 
medullary  sheaths  being  destroyed  (broken  down  into  myelin  and 
fat  droplets)  ;  but  the  neurolemma  and  its  nuclei  remain  intact 
(Nasse,  Waller,  Lent,  Benecke  and  others).  The  degeneration 
may  also  extend  centrally  in  the  divided  nerve  for  the  distance  of 
one  segment   (to  the  first  node  of  Ranvier).     Conductivity  ceases 


Regeneration  of  Nerves. 


249 


instantly  when  continuity  is  interrupted  (provided  there  are  no  col- 
lateral paths).  The  space  intervening-  between  the  central  and  periph- 
eral portions  is  filled  at  first  with  fibroplastic  cicatricial  tissue ; 
but  later  a  complete  regeneration  of  the  nerve  fibres  is  accomplished 
and  in  the  course  of  two  or  more  months  the  nervous  function  is 
fully  reestablished.     This  later  development  of  the  nerve  fibres,  as 


Fig.  45. 

Degenpi-ation  of  nerve  fibres  after  sec- 
tion. I.  normal  nerve  fibre.  II  and  III. 
different  degrees  of  destruction.  S. 
nein-filemma  slieatli  of  Scliwann.  ///, 
medullary  slieatb.  A,  axis  cylinder.  7.-, 
nucleus  of  neurolemma.  L.  Lanter- 
mann's  constriction  of  the  medullary 
sheath,  int.  myelin  gloliules.  «.  remains 
of  axi.s  cylinder,  w,  proliferating  cells 
of  neurolemma.  Partly  schematic.  X  476. 
(After  Thoma.) 


§  |i 


Fig.    4G. 

Growths  of  the  axis  cylinder  in  the 
central  stump  of  a  divided  nerve.  aS'. 
neurolemma  sheath  of  Schwann,  m, 
medullary  sheath.  A,  axis  cylinder  of 
undegenerated  part  of  the  nerve.  A'. 
newly  formed  axis  cylinder,  fc,  nucleus 
of  neurolemma.  ir,  ic,  proliferated 
neurolemma  cells,  mt,  myelin  globules. 
Scliruiatic,  based  on  an  illustration  from 
Eichhorst.      X    470.      (After  Thoma.) 


indicated  b\-  the  microscopic  findings,  which  are  demonstrable  with 
much  difficulty,  may  be  explained  in  two  ways.  The  majority  of 
investigators  adhere  to  the  views  advanced  by  Waller  and  Strobe, 
according  to  whicl;i  regeneration  is  the  result  of  a  growth  of  the 
axis  cylinders  of  the  central  stump,  these  advancing  into  the  young 
cicatricial  mass  and  growing  beyond  it,  the  delicate  fibres  of  the 


250  Regeneration. 

axis-cylinders  meanwhile  undergoing  subdivision.  It  is  a  striking 
phenomenon  in  this  process  that  the  newly  formed  fibres  of  a  divided 
nerve  should  grow  into  the  original  areas  of  distribution.  The 
opinion  most  nearly  explaining  this  assumes  that  the  old  paths  of 
distribution  persist  as  actually  empty  tubes,  or  as  the  neurolemma 
tubes  of  Schwann  containing  merely  a  softened  fatty  detritus,  and 
that  the  sprouts  of  axis  cylinder  substance  find  here  the  line  of  least 
resistance  in  their  penetration.  It  has,  however,  been  shown  that 
after  resection  the  nerve-sprouts,  in  spite  of  the  insertion  of  special 
interfering  objects,  follow  along  their  original  direction;  and  the 
interesting  experiments  of  Forsmann  show  that  the  nerve  stump 
will  not  invariably  push  its  way  into  empty  glass  tubes  which  have 
been  inserted  but  will  on  the  contrary  always  force  its  sprouts  into 
glass  tubes  containing  nerve  or  brain  substance,  even  if  these  be  ar- 
ranged in  the  wrong  direction.  It  seems  probable  therefore  that 
chemotactic  force,  exerted  by  the  degenerating  nerve  matter  of  the 
peripheral  portion  of  the  nerve,  determines  the  line  of  extension  of 
the  growing  nerve  fibres  (neurotropism). 

The  force  of  growth  of  the  central  stump  is  usually  very  marked. 
V'anlair  succeeded  in  enclosing  calcareous  tubes,  made  of  bone,  be- 
tween the  two  ends  of  a  divided  nerve,  and  the  growing  sprouts  not 
only  found  their  way  into  the  lumen  of  the  tubes,  but  even  into  the 
Haversian  canals  (Thoma).  Sometimes  the  budding  axis  cylinders 
form  tumor-like  masses  in  the  scar  tissue  around  the  stump,  the  so- 
called  amputation  neuromata. 

As  the  neurolemma  with  its  nuclei  remains  intact  in  the  degen- 
erated peripheral  fibres,  it  is  possible  that  the  formation  of  new 
medullary  substance  may  arise  from  this  source  in  case  the  new 
axis  cylinders  grow  into  these  preformed  paths.  Proliferative  phe- 
nomena in  the  cells  of  the  neurolemma  have  been  actually  observed 
(Eichhorst,  L.  Mayer,  v.  Bi^ingner),  and  consequently  the  view  is 
held  that  this  sheath,  by  dififerentiation  of  its  protoplasm,  may  give 
rise  in  segments  to  the  axis  cylinder  and  medullary  sheath ;  that 
in  this  way  from  the  old  sheath  new  nerve  fibres  may  be  formed, 
the  segments  then  growing  together  to  form  continuous  threads. 

Ganglionic  cells  and  the  massive  nervous  tissue  of  the  brain  and 
cord  are  incapable  of  regeneration.  It  is  well  known  from  numer- 
ous experiments  upon  animals  and  studies  in  man  in  connection 
with  injuries,  partial  ablations  and  other  types  of  loss  of  substance, 
as  from  haemorrhage,  degeneration,  etc.,  that  even  in  case  the  usual 


Transplantation.  251 

fatal    complications    do    not    develop    such   lesions    do    not   end    in 
new  formation  of  nervous  elements  but  in  fibroplastic  cicatrization. 

Regeneration  of  Blood  Corpuscles  and  Lymph  Cells. — The  resto- 
ration of  blood  cells  does  not  take  place  within  the  blood  vessels,  but 
originates  in  those  organs  in  which  normally  the  continual  replace- 
ment of  worn  out  cells  of  the  blood  and  lymph  is  accomplished,  par- 
ticularly the  bone  marrow,  spleen,  lymph  nodes  and  in  lymphoid 
germinal  foci  scattered  about  in  various  tissues.  The  red  blood 
corpuscles  develop  entirely  from  cells  of  the  medulla  of  bones  and 
are  nucleated  when  first  formed ;  b}'  the  time  they  have  entered  the 
circulation  their  nuclei  have  disappeared.  Serious  or  repeated  loss 
of  blood  cells  calls  forth  so  marked  a  proliferation  of  the  hemo- 
poietic marrow  tissue  that  the  fatty  marrow  of  the  long  bones  comes 
to  resume  its  embryonic  character  and  is  changed  into  red  marrow. 
The  colorless  corpuscles  are  produced  by  proliferation  of  the  leuco- 
cvtes  and  Ivmphocvtes  in  the  structures  mentioned  and  pass  out  into 
tlie  blood. 

The  fluid  portion  of  the  blood  is  renewed  by  the  passage  of 
water  and  salts  from  the  tissues  into  the  lymph  and  blood  capilla- 
ries. 

Transplantation. 

Some  cells  and  tissues  can  maintain  their  vitality  for  some  time 
after  their  removal  from  the  animal  body  and  are  capable  of  renew- 
ing their  growth  if  artificially  implanted  upon  another  part  of  the 
same  body  or  in  another  animal.*  Experiments  in  transplanation 
have  been  performed  frequently  and  sometimes  successfully  by 
surgeons  ever  since  the  fifteenth  century,  for  the  purpose  of  re- 
storing denuded  parts  of  the  skin  and  other  tissues  in  man ;  and, 
too.  the  same  experiments  have  been  repeatedly  performed  in  ani- 
mals in  order  to  obtain  theoretical  grounds  for  operative  procedures 
and  explanations  of  pathological  questions. 

It  is  most  easilv  and  successfully  performed  in  lower  animals. 
Born  has  succeeded  in  causing  adhesive  growth  in  pieces  cut  rflf 
from  larval  amphibians  to  take  place  in  various  ways,  as  of  the 
head  end  of  one  larva  to  the  tail  end  of  another.  Joest  succeeded 
in  uniting  the  opposite  ends  of  earthworms.  As  interesting  trifles, 
after  the  castration  of  cocks  the  spurs  used  to  be  often  cut  off  and 

*  Inoreranic  particles,  as  bits  of  ivory,  wire  or  bullets,  if  they  get  into  or 
are  introduoed  into  the  tissues  (implantation.  Insertion)  may  be  encapsulated, 
that  is.  surrounded  bv  connective  tissue.  Even  living-  or  dead  tissues  may 
be  similarly  surrounded,  as  an  extracted  tooth  may  be  thus  held  in  an  alveolus 
in  which  it  is  implanted.  In  transplantation,  also  known  as  grafting  (French, 
<i>Tffe).  there  is  not  merely  an  encapsulation  or  adherence  of  the  tissue 
to  the'  structure,  but  in  addition  it  multiplies  in  the  site  of  Implantation  and 
forms  part  of  the  organic  structure   with  the   tissue  about  it. 


252  Transplantation. 

inserted  into  a  split  in  the  comb  of  the  capon,  becoming  attached 
by  growth  in  this  situation  (Aldrovandi,  Worm,  in  the  seventeenth 
century ;  Baronio  in  1804).  The  spur,  if  engrafted  when  very  young, 
may  grow  in  this  new  and  well  vascularized  base  to  become  several 
inches  in  length ;  and  sometimes  tlie  central  bony  core  grows,  carry- 
ing over  it  a  horny  epidermal  covering,  so  as  to  produce  two  spurs 
growing  alongside  of  each  other.  Embryonic  tissue  with  undiffer- 
entiated cells  shows  a  moderate  capacity  for  growth  when  trans- 
planted. Fere  grafted  bits  of  blastoderm  (forty-eight  hours)  and 
the  eyes  of  six  to  eight  day  chick  embryos  under  the  skin  of  young 
chickens  and  noted  that  the  mesoblastic  tissue  underwent  more  or 
less  further  development  to  the  production  of  small  tumors  (con- 
taining cartilage  and  in  one  case  small  feathers),  which  persisted  for 
about  a  month.  Such  a  result  has  an  important  bearing  in  explain- 
ing the  conditions  involved  in  the  origin  of  tumors. 

Transplantation  of  tissues  is  more  difficult  in  mammals.  The 
possibility  is  best  realized  when  the  part  to  be  transplanted  can 
retain  connection  with  its  neighboring  structures  by  a  bridge,  as 
where  a  flap  of  skin  is  twisted  around  and  stitched  to  an  adjoining 
part,  the  nutrition  of  the  flap  being  at  least  partially  maintained 
(as  in  the  operation  of  rhinoplasty  in  man).  The  result  in  trans- 
planting unattached  and  completely  separated  bits  of  the  corium 
and  of  the  epiderm  is  not  at  all  uniform.  In  this  procedure,  recom- 
mended by  Reverdin  and  Thiersch  for  quickly  obtaining  an  epi- 
dermal surface  over  large  superficial  wounds,  which  has  been  tested 
by  many  investigators,  especially  by  ]\Iarchand  and  Enderlin  experi- 
mentally, the  transplanted  fragments  adhere  by  a  layer  of  coagulated 
blood  and  lymph  to  the  fresh  or  granulating  wound.  Later  on  there 
occurs  an  active  vascular  and  cellular  proliferation  in  the  substruc- 
ture, the  fibroblasts  and  angioplasts  of  the  latter  growing  up  into 
and  through  the  engrafted  cuticular  fragment,  which  is  actually  re- 
placed by  the  new  connective  tissue.  The  epithelium  desquam- 
ates and  only  to  a  very  slight  extent  is  the  graft  the  starting  point 
for  the  formation  of  the  new  layer  of  skin.  In  reality  the  new 
graft  is  more  like  a  piece  of  plaster,  beneath  which  the  formation 
of  new  elements  from  the  adjacent  structures  may  take  place  with 
facility  (Diirk).  For  success  in  such  transplanations  the  size  of 
the  bit  of  tissue  transplanted  should  be  taken  into  consideration 
(even  particles  no  larger  than  a  pea  may  disintegrate  in  the  central 
part  because  too  much  time  is  required  to  afford  them  proper  nour- 
ishment), as  well  as  the  question  whether  the  base  of  implantation 
affords  thoroughly  favorable  conditions  for  nutrition.    For  example 


Transplantation  of  Skin  and  Glands.  253 

suppuration  of  the  granulating-  surface  interferes  with  proper  at- 
tachment; and,  as  the  function  of  the  tissue  depends  greatly  upon 
nervous  influences  growth  of  a  transplanted  fragment  is  sometimes 
prevciited  because  of  the  lack  of  any  natural  nervous  comnuniica- 
tion.  Again  the  portion  to  be  transplanted  ought  to  be  kept  as 
nearly  as  possible  at  its  proper  vital  temperature  (tissues  have  been 
successfully  grafted,  however,  even  after  having  been  ke]it  for 
from  one  to  four  days). 

While  transplantation  of  bits  of  skin  to  new  positions  in  the 
same  individual,  as  to  the  ear  in  a  rabbit,  has  met  with  fair  suc- 
cess, attempts  to  graft  from  one  individual  to  another  have  not 
been  so  successful ;  and  transplantation  from  the  skin  of  an  animal 
to  man  has  failed  in  most  instances.  Efforts  to  transplant  mucous 
membranes  (that  of  the  lip  to  the  lid)  and  of  keratous  tissues  (in 
the  repair  of  corneal  lesions),  both  in  man  and  animals,  have  shown 
little  uniformity.  In  transplanting  cartilage,  periosteal  and  bony  tis- 
sue the  graft  as  a  rule  persists  for  a  long  time  and  there  may  be 
noted  a  certain  amount  of  increase  of  the  cartilaginous  and  perios- 
teal cells.  However,  this  is  not  active  enough  to  permit  it  to  be 
said  that  there  is  an  artive  part  taken  by  the  graft  in  the  repair  of 
an  existing  lesion  ;  but  rather  that  the  fibroblasts,  angioplasts  and 
osteoplasts  at  the  border  of  the  lesion  grow  into  the  transplanted 
tissue  and  gradually  take  its  place.  Inasmuch  as  the  transplantation 
of  such  material  (small  fragments  or  pieces  of  bone,  the  length  of 
a  finger,  not  necessarily  fresh  bone  but  with  equally  good  results 
in  the  use  of  macerated  or  boiled  bone  or  bone  sterilized  by  heat) 
may  materially  aid  and  hasten  the  restoration  of  a  given  defect 
and  the  formation  of  a  solidly  ossified  scar  in  it.  the  method  has 
gained  considerable  importance  in  surgery. 

Experiments  by  Ribbert.  Lengemann,  Lubarch  and  Enderlen 
have  proved  that  transplantation  of  small  pieces  of  salivary  glands, 
sebaceous  glands,  mammary  tissue,  thyroid  gland,  epididymis,  ova- 
rian tissue,  and  liver  tissue  into  the  peritoneal  cavity,  anterior  cham- 
ber of  the  eye.  under  the  skin  and  within  the  lymph  glands,  is  fol- 
lowed by  more  or  less  perfect  adhesive  growth  and  actual  prolifera- 
tion of  the  glandular  epithelium,  with  formation  of  new  cellular 
extensions  with  development  of  gland  spaces  and  persistence  of  the 
vitality  of  the  transported  tissue.  Ribbert's  graft  of  mammary 
gland  tissue  into  the  ear  of  a  young  guinea  pig  has  special  interest 
from  the  fact  that  when  the  animal  bore  young  the  transplanted 
gland  began  to  secrete  milk. 


254  Hypertrophy. 

Operative  grafting  of  thyroid  tissue  in  case  of  loss  of  this  organ 
(as  in  goitre  and  operation  for  the  removal  of  goitre),  which  is 
apt  to  cause  serious  and  even  fatal  disease,  may  successfully  com- 
pensate for  the  loss  and  is  therefore  of  value  from  a  therapeutic 
point  of  view.* 

Hypertrophy.     G-igantism. 

By  the  term  liypcrtrophy  is  meant  the  increase  of  the  essential 
tissue  of  a  part  of  the  body,  leading  to  enlargement  of  that  part. 

Literally  the  term  reallj-  means  excess  of  nutrition  {virep  and  Tp6(pos, 
nutrition),  and  from  ancient  times  it  -.vas  used  to  express  increase  in 
volume  of  tissues  and  organs  when  it  was  supposed  that  this  depended 
upon  an  increase  of  the  nutritive  supply  to  the  ::tructure  involved.  Theo- 
retically and  from  the  microscopic  findings,  two  types  of  increase  in 
volume  may  be  conceived  of :  hypertrophy,  in  which  the  cellular  elements 
are  seen  to  be  increased  in  size,  and  hyperplasia,  where  a  numerical 
increase  in  the  cells  is  the  b.'isir,  for  the  increase  in  the  c'imtnsions  of 
the  organ.  [These  are  often  spoken  of  as  simple  hypertrophy  and  numeri- 
cal hypertrophy.! 

Where  the  increase  of  tissue  involves  the  functionating  elements 
of  an  organ  or  part,  as  the  parenchyma  of  a  gland  or  the  muscle 
cells,  it  is  spoken  of  as  true  hypcrtropliy;  where,  however,  it  con- 
sists in  an  increase  of  the  supporting  tissue  or  so-called  interstitial 
substance  alone  (connective  tissue,  fat)  it  is  a  false  hypertrophy. 

True  hypertrophies  occur  because  of  increased  demands  upon 
the  activities  of  an  organ  and  because  of  its  increased  functional 
effort.  Such  examples  are  termed  ivork  hypertrophies.  This  is  most 
frequently  seen  in  muscles,  a  very  common  example  being  met  in  the 
increase  in  the  skeletal  muscles  in  gymnasts  and  the  arm  muscles  of 
wood  choppers  and  smiths.  The  increased  cardiac  force  in  those 
conditions  of  life  in  man  and  animals  requiring  continuously  special 
power  of  the  heart  is  an  expression  of  an  hypertrophy.  The  heart 
possesses  in  a  marked  degree  the  power  of  accommodation  to  in- 
creased demands  upon  its  ability ;  its  muscular  substance  in  case 
of  permanent  increase  of  labor  increases  {accommodative  hyper- 
trophy) up  to  a  certain  degree,  determined  largely  by  the  relation 
to  the  body  weight.  According  to  tlie  investigations  of  Bollinger 
and  Parrot  all  animals  wdiich  are  required  to  exert  much  muscular 
energy  because  of  their  mode  of  life  possess  a  heart  heavier  in 
proportion  to  the  body  weight  than  those  animals  which  lead  a 
sluggish  life,  as  the  dog  in  comparison  with  the  hog,  the  deer  in 

*  In  man  thyroid  preparation.s  may  be  administered  by   the   mouth. 


Compensatory  Hypertrophy.  255 

comparison  with  the  sheep.  There  are  marked  differences  in  this  con- 
nection between  those  birds  which  are  good  fliers  and  the  domes- 
tic fowls  which  stay  more  on  the  ground.  (For  details  cf.  Kitt, 
Pathol.  Anatomic  dor  Haustierc,  11  Bd.  Chapter  on  the  Heart. 
\ei-l.  V.  F.  Enke,  Stuttgart.     II  Aufl.  1901.) 

All  diseases  which  increase  the  work  of  emptying  the  ventricles 
of  the  heart  in  the  period  of  systole  and  which  force  the  heart  to 
continuously  increased  pumping  effort,  give  rise  to  cardiac  hyper- 
trophies, usually  confined  to  one  part  of  the  organ  according  to  the 
position  of  the  opposition  to  the  cardiac  effort.  Chronic  valvular 
lesions,  which  interfere  with  the  ready  passage  of  the  blood  from  the 
auricles  into  the  ventricles,  after  a  primary  dilatation  of  the 
auricles  cause  hypertrophy  of  the  auricular  walls;  stenosis  of  the 
semilunar  aortic  valves  causes  hypertrophy  of  the  left  ventricle, 
stenosis  of  the  pulmonar}-  valve  a  hypertrophy  of  the  right  ventricle  ; 
It  is  only  by  a  heightened  muscular  force  that  the  blood  can  be 
pressed  forward  in  such  conditions.  If  the  cardiac  hypertrophy 
is  for  a  long  time  sufficient  to  accomplish  the  increased  demands 
put  upon  its  functional  capability  and  thus  prevents  the  serious 
results  of  tlie  original  disease  or  compensates  for  them,  it  is  spoken 
of  as  a  compensatory  hypcrtropJiy. 

Smooth  muscles  also  become  hypertrophied  in  case  of  increase 
of  function,  physiologically  seen  in  the  pregnant  uterus,  patholog- 
ically observed  in  marked  degree  in  the  intestinal  wall  where  con- 
strictions in  the  lumen  gradually  develop,  over  which  the  chyme  can 
be  driven  only  by  increased  peristaltic  force.  The  same  thing  is 
seen  in  case  of  the  urinary  bladder,  resulting  from  narrowing  of 
the  neck  of  the  viscus  by  prostatic  enlargements  or  from  involve- 
ment by  urinary  calculi,  etc. :  and  in  the  oesophagus  in  case  of  stric- 
tures. In  all  these  cases  there  occurs  both  a  multiplication  and  an 
increase  in  size  of  the  muscle  cells. 

In  the  glands  of  the  body  true  hypertrophy  and  the  necessity  for 
increased  effort  become  apparent  where  smaller  or  larger  portions 
of  the  glandular  parenchyma  are  destroyed,  and  are  restored  or  re- 
placed by  regeneration.  In  case  this  cannot  fully  obtain  or  does 
not  occur  at  all,  as  in  the  liver  tissue  (after  echinococcosis  or  chron- 
ic inflammations)  the  remaining  portions  of  the  organ  become  en- 
larged and  the  general  volume  of  the  liver  may  thus  become  greater 
than  normal.  Especially  in  case  of  bilateral  organs  where  one  be- 
comes entirely  incapable  of  function,  the  remaining  one  acts  for 
the  former,  performs  a  correspondingly  greater  amount  of  work 
and  hypertrophies  (compensatory  or  vicarious  hypertrophy).  Where 


256  Hypertrophy. 

one  kidney  is  removed  in  an  experiment,  in  the  course  of  but  a  few 
days  thereafter  the  other  begins  to  enlarge ;  and  it  is  not  infrequent 
in  slaughtered  animals  to  find  one  kidney  shrunken  up  and  the  other 
from  one  to  two-thirds  larger  than  the  normal  organ.  The  reason 
that  the  increase  in  volume  does  not  reach  double  the  normal  is 
because  all  of  the  constituent  elements  do  not  hypertrophy  in  even 
proportion,  the  process  involving  particularly  tlie  secretory  struc- 
tures, the  glomeruli  and  the  convoluted  tubules,  the  epithelial  cells 
of  w^hich  enlarge  and  the  coils  become  more  intricately  convoluted 
and  therefore  longer.  Of  course  compensation  for  a  functional  dis- 
turbance of  a  gland  by  hypertrophy  can  result  only  in  case  there 
exist  analogous  tissue  or  a  glandular  rest."-^'  In  this  sense  the 
lymph  glands  and  the  bone  marrow,  for  example,  might  substitute 
for  loss  of  the  spleen,  but  not  other  kinds  of  glands. 

As  a  reason  why  glandular  organs  are  forced  to  higher  secretory 
activity  in  case  of  removal  of  a  portion  of  their  parenchyma,  it  may 
be  assumed  that  following  the  ablation  of  the  organic  parenchyma 
there  accumulate  in  the  blood  certain  secretory  stimulants,  sub- 
stances which  stimulate  the  gland  cells.  \\'hether  these  substances 
act  directly  on  tlie  protoplasm  to  stimulate  it  to  productive  activity, 
or  whether  the  more  active  protoplasm  takes  up  more  nutritive  ma- 
terial and  is  therefore  enabled  to  throw  off  more  products,  is  un- 
certain (Ribbert).  The  fact  that  muscles  in  a  state  of  increased 
activity  receive  an  augmented  blood  supply  and  in  case  of  destruc- 
tive changes  in  an  organ  a  similar  hypersemia  develops  in  its  remain- 
ing tissue  (due  to  the  accumulation  of  materials  no  longer  se- 
creted) suggests  according  to  Ribbert  an  explanation  for  the  oc- 
currence of  hypertrophy,  in  that  the  persistent  congestion  distends 
the  tissue,  with  the  result  of  separating  the  individual  cells  from 
each  other  and  thus  gives  origin  to  space  for  the  increase  of  vol- 
ume and  for  the  multiplication  of  cells.  Not  only  is  it  to  be  sup- 
posed that  free  spaces  exist  between  the  cells  but  the  protoplasm 
itself  is  substantially  distended,  its  individual  molecules  separated 
from  each  other  and  this  intracellular  increase  of  space  affords  op- 
portunity for  assumption  of  further  elements  which  go  to  make 
up  the  protoplasm.  Ribbert's  theory  of  mechanical  origin  of  tissue 
growth  (cf.  Regeneration)  finds  special  applicability  in  the  devel- 
opment of  cardiac  hypertrophy  and   the  hypertrophy  of  muscular 

♦  [What  is  meant  here  is  the  persistence  in  undeveloped  form  of  tissue 
capable  of  taking  up  the  morpholoR>'  and  function  ot  the  adult  tissue  which 
has  been  lost.  TTnus  in  the  formation  of  an  organ  there  may  be  embryonic 
elements  in  excess  which  are  not  employed  in  the  formation  or  subsequent 
development  of  the  organ,  remaining-  as  "rests"  and  undifferentiated.  In 
case  of  loss  of  substance  of  the  organ  such  representatives  may  perhaps  develop 
to  maturity  and   compensate  for   the  destroyed  portions.] 


I'acunm,  Xcn'ous,  / iillniiiiitatory  11  ypcrtroplix.  257 

canals  (vessels,  intestine,  nrinarx-  liladder  or  i^iillet ) .  the  cause  in 
such  instance  always  heing  a  retention  of  the  contents  ( increase 
of  blood  pressure,  influence  of  calculi,  obstruction  to  the  movement 
of  tlie  chyme,  etc.)  causing  primarily  distension  of  the  lumen  of 
the  part  and  stretching  of  the  muscular  wall. 

That  a  diminution  of  the  factors  of  resistance  of  growth,  of  tissue 
resistance,  favors  hypertrophy  (z'aciiuin  hypertrophy)  is  apparent 
in  the  liver  in  case  of  the  existence  of  a  diaphragmatic  cleft ;  the 
liver  tissue  invariably  grows  through  such  an  opening,  and,  just  as 
a  button  goes  through  a  liutton  hole,  forms  a  new  liver  lobe  pro- 
truding into  the  thorax,  the  soft  and  elastic  lung  tissue  ofifering  but 
little  opposition.  Such  intrathoracic  hepatic  lobes  may  sometimes 
be  found  larger  than  a  fist  (in  sheep,  cattle,  swine). 

[The  influence  of  nervous  factors  in  some  cases  of  hypertrophy 
can  scarcely  be  doubted,  although  it  is  probable  that  for  the  most 
part  such  influence  operates  in  ways  conforming  with  the  causes 
above  mentioned.  The  ability  to  take  up  and  assimilate  nutrition 
is  in  relation  with  the  trophic  influence  of  the  nervous  system,  and 
the  condition  of  the  vessels  supplying  nutrition  has  even  more  ap- 
parent dependence  upon  the  nervous  functions ;  and  so,  too,  the  rela- 
tive tone  or  the  opposite  condition  of  relaxation  of  tissues  is  regu- 
lated by  nervous  factors.  Variations  in  functional  activity  are  often 
determined  by  nervous  influences.  Leaving  aside  such  influences 
in  which  perhaps  the  nervous  factor  may  determine  hypertrophy 
by  evident  involvement  of  such  influences  as  increase  of  blood  sup- 
ply, the  provision  of  mechanical  relaxation  of  tissue  or  the  stimu- 
lation of  functional  activity,  there  are  more  obscure  examples  (pos- 
sibly in  the  end  explicable  on  the  same  grounds  but  not  clearly 
showing  such  reasons  for  growth)  which  for  the  time  are  properly 
spoken  of  as  nervous  hypertrophies,  as  the  enlargements  in  acro- 
megaly, for  example,  or  the  papillary  enlargements  of  the  skin  in 
many  warts.] 

Connective  tissue  hypertrophies  are  usuall}-  the  result  of  chronic 
inflammation  and  chronic  passive  hyperaemia.  in  either  of  which 
there  are  features  of  tissue  destruction  and  of  tissue  dilatation. 
Where  the  liver  becomes  enlarged  and  the  seat  of  connective  tissue 
induration  from  chronic  inflammation  there  occurs  primarily  a  de- 
struction of  the  liver  cells  and  a  coincident  growth  of  the  support- 
ing tissue ;  the  termination  of  chronic  lymphangitis  of  the  cellular 
tissue  of  the  foot  in  pachydermia  (rufifle  foot  or  bristle  foot  in  the 
horse)  may  be  explained  by  the  idea  that  at  first  the  connective 
tissue  spaces  are  filled  with  lymph  and  exudate  and  later  become  oc- 


258  Inflanunation. 

cupied  by  the  proliferating  connective  tissue.  The  formation  of 
thick,  keratous  epidermal  layers  (keratoses)  over  callosities  of  the 
skin  or  inflamed  and  distended  bursje  is  to  be  ascribed  less  to  the 
direct  influence  of  external  pressure  than  to  the  pressure  exerted 
from  beneath  by  the  hard  and  thickened  cutis  upon  the  epiderm 
(see  also  chapters  on  Regeneration  and  Inflammation). 

The  occurrence  of  congenital  hypertrophies  of  certain  parts  of  the 
body  may  be  due  to  a  number  of  causes.  Some  examples  are  compen- 
satory hypertrophies,  as  when  one  kidney  fails  to  develop  the  other  grows 
to  unusual  size;  others  are  due  to  chronic  passive  hyperemia  in  the  foetus 
caused  by  constrictions  by  amniotic  bands,  as  the  hypertrophy  of  the  pinna 
of  the  ear  or  of  the  penis,  (cf.  Chapter  on  i\ialformations,  Spcziellc 
patJiol.     Anatomic   der  Hausticre,   I    Bd.). 

Inflammation. 

The  term  inflammation  is  applied  to  a  condition  of  local  irrita- 
tion  of  the  tissues,  the  seat  of  some  type  of  injury,  in  which  there 
occur,  as  phenomena  of  reaction  to  the  irritant,  changes  in  the 
blood  current  and  lymphatic  floiv,  exudation  of  the  constituents  of 
the  blood,  excessive  secretion  of  glands,  phagocytosis  and  prolifer- 
ation of  the  tissues. 

In  dealing  with  inflammation  we  have  to  do  with  a  series  of 
processes  which  are  nothing  more  than  modifications  and  exaggera- 
tions of  physiological  procedures,  in  this  case  having  for  their  ob- 
ject the  defense  of  the  organism  against  the  harmful  influences  and 
the  compensation  for  local  disturbances  of  nutrition,  and  represent- 
ing abilities  of  the  animal  organism  acquired  through  phylogenetic 
adaptation.  (Leber,  Aletschnikoff,  Diirk,  ]\Iarchand,  Schmauss  and 
otliers). 

In  the  lowest  unicellular  organisms,  as  the  amcebae,  the  phe- 
nomena of  reaction  to  harmful  influences  are  manifested  by  the 
properties  of  chemotaxis,  phagocytosis  and  intracellular  digestion. 
In  the  more  highly  organized  forms  of  life,  made  up  of  dififerentiated 
cells,  these  defensive  functions  are  assumed  by  certain  groups  of 
cells  (Diirk)  ;  and  in  conformity  with  the  complexity  of  structure 
and  interdependence  of  tissues  and  organs  and  the  variability  of 
the  injuries,  these  regulative  and  reparatory  processes  are  made  up 
of  a  number  of  separate  phenomena  which  in  their  synchronous 
and  consecutive  operations  are  grouped  together  under  the  com- 
prehensive term,  inflammation. 

In  the  class  of  harmful  agents  capable  of  inducing  inflammation, 
the  causes  of  intlannnation  or  irritants,  are  included  a  great  variety 


Causes  of  Iiiflamination.  259 

of  foreign  bodies,  parasites,  infectious  substances,  poisons  and  ther- 
mic   influences  which    arc    spoken    of    as  external  eaitses.     These 
do  not  act  in  reahty  as  the  immediate  causes  of  the  process  but 
produce  primarily  some  type  or  other  of  tissue  change,  as  necroses, 
degenerations  and  injuries,  and    the    inflammatory  reaction    is    di- 
rectly    due     to     an     effort     to     compensate      for      these      latter. 
[It  is  not  the  heat  of  the  flame  or  the  steel  of  the  knife  which 
actually  causes  the  inflammation  ;  these  are  probably  at  once  with- 
drawn.    They,  however,  alter  the  cells  and  tissues,  and  the  inflam- 
matory reaction  arises  in  reality  to  eliminate  or  isolate  these  altered 
structures  and  prevent  their  acting  as  irritants,  and  to  make  re- 
pairs for  their  loss..]    One  and  the  same  influence,  depending  upon 
the  intensity  and  duration  of  its  operation,  may  be  responsible  for 
a  number  of  types  of  tissue  alteration;  an  irritant  poison,  an  acid, 
may  in  different  degrees  of  concentration,  heat  or  cold,  give  rise 
perhaps  to  a  simple  hyper?emia,  to  a  superficial  inflammation  or  to 
deep  ecshars.     Strictly  speaking  tissue  necrosis  is  always  produced, 
sometimes  only  superficially,  affecting  only  epithelium  and  vascular 
endothelium  and  essentially  microscopic  in  extent,   at  other  times 
extending  more  deeply  or  involving  decidedly  larger  areas  and  ap- 
preciable to  the  unaided  eye.     In  the  first  instance  reparation  is  ac- 
complished so  quickly  b}-  phagocytosis  and  prompt  regeneration  that 
the  full  picture. of  inflammation  is  not  developed,  these  two  factors 
of  inflammation  alone  occurring  in  the  tissue;  in  case  of  the  de- 
struction of  a  larger  amount  of  tissue,  however,  provided  it  is  not 
fatal  directly  or  from  complicating  infection  and  putrefaction,  the 
inflammatory  reaction  with  its  entire  group  of  phenomena  results. 
A  given  infectious  agent  may  in  one  case  give  rise  to  a  rapid  general 
infectious  process  with   fatal  termination  or  in  another  only  to  a 
typical  local  inflammation,  as  illustrated  by  the  varying  effects  of 
bacillus  anise pticus  in  the  virulent  or  attenuated  state  and  in  the 
particular  state  of  individual  predisposition  of  the  subject.      In  reality 
the  animal  body  reacts  to  all  physical  and  chemical  injuries  by  the 
production  of  an  inflammatory  process,  provided  time  be  afforded; 
that  is.  provided  the  injury  does  not  involve  a  vital  tissue  or  organ 
to  such  a  degree  as  to  immediately  produce  death  from  the  func- 
tional   disturbance.      Where    bacteria    of    extreme    virulence,    with 
haemolytic  power  and  capable  of  rapid  extension,  invade  the  sys- 
tem, a  bacteriasmia  or  toxic  infection  is  said  to  exist ;  in  such  cases 
there  is  not  enough  time  permitted  for  compensation  by  an  inflam- 
matorv  reaction  for  the  disturbances  occasioned.     Were  the  micro- 
organisms of  lower  virulence,  did  they  multiply  more  slowly  at  the 


26o  Iiiflamuwtion. 

focus  of  infection  so  that  their  toxines  might  be  restrained  or  ren- 
dered in  some  measure  inert,  or  if  the  animal  body  be  especially 
well  provided  with  bactericidal  substances,  the  course  of  the  disease 
would  be  protracted  and  there  would  be  time  for  the  tissue  to  set 
into  activity  some  or  all  of  the  reactions  belonging  to  the  inflam- 
matory process.  Inflammation  may  therefore,  as  the  combined  man- 
ifestation of  a  number  of  defensive  efforts  directed  against  harm- 
ful agencies,  be  looked  upon  as  a  curative  process.  When  the  forces 
brought  into  activity  succeed  in  eliminating  the  source  of  harm  the 
inflanmiation  reaches  in  a  relative  measure  its  physiological  termi- 
nation (Diirk )  ;  when,  however,  the  reaction  directed  to  the  removal 
of  harmful  influences  is  not  successful  in  elimijiating  them,  when, 
perhaps,  the  latter  multiply  in  the  system,  the  organism  perishes  in 
spite  of  the  inflammation,  not  necessarily  because  of  the  inflamma- 
tion but  because  of  the  infection  or  intoxication,  or  possibly  actually 
because  of  the  inflammatory  reaction  from  the  series  of  functional 
disturbances  of  the  organs  resulting  from  its  onset. 

The  Phenomena  of  Inflammation, — From  the  earliest  centuries 
of  our  era,  when  the  Roman  physicians  Celsus  and  Galen  at- 
tempted to  formulate  a  conception  of  inflammation,  there  have 
been  recognized  as  cardinal  symptoms  of  the  process  in  the 
grossly  visible  parts  of  the  living  body:  increased  heat,  redness, 
szvellinj:^-  and  increased  sensifiTcness  of  the  inflamed  part  (calor. 
rubor,  tumor,  dolor),  to  which  may  be  added  disturbance  of 
fnncfion  {fnnctio  Jccsa)  as  a  fifth.  These  fundamental  symptoms 
are,  it  is  true,  clearly  appreciable  in  most  acute,  that  is,  rapidly 
developed,  inflammations  of  the  skin  and  mucous  membranes ; 
but  they  are  not  invariably  to  be  noted  in  the  entire  course  of  the 
process.  The  older  the  inflammation  becomes,  the  more  likely  are 
these  features  to»be  lost  one  after  another ;  and  a  chronic  inflamma- 
tion beginning  gradually  and  continuing  in  low  grade  may  not  show 
anv  of  them.  Moreover  the  supposition  that  internal  organs  in  in- 
flammation show  the  same  intense  redness,  swelling,  increase  of 
temperature,  and  increased  sensibility  to  pain,  is  only  partly  correct ; 
and  here  too  the  chronic  inflammations  are  especially  likely  riot  to 
be  characterized  by  such  phenomena. 

In  the  efifort  to  analyze  the  nature  of  inflammation  from  an 
anatomical  standpoint  modern  studies,  have  furnished  definite  ex- 
planations of  the  above  mentioned  symptoms  of  Galen  and  have 
given  sufficient  insight  into  the  inflammatory  process  to  afiford  a 
fairlv  precise  knowledge  of  the  character  of  the  changes  and  the 
methods  followed  bv  the  tissues  in  their  inflammatory  reactions  to 


Phenomena  of  I)ifIaim)iatioii. 


261 


irritants.  Thanks  to  the  studies  of  Mrchow,  Recklinghausen, 
Cohnheim,  Ziegler,  Alarchand  and  others,  the  various  steps  which 
develop  and  take  part  in  the  process  in  inflamed  tissues  have  come 
to  be  well  understood.  Only  in  connection  wnth  relatively  unim- 
portant questions  do  there  still  exist  differences  of  opinion  and  theo- 
retical discussions,  involving-  for  instance  such  points  as  whether 
the  proliferation  attending  inflammation  is  produced  by  excess  of 
nutrition  or  lack  of  tissue  tension,  whetlier  it  may  be  assumed  or 
not  that  there  is  a  functional  stinmlation  to  excite  cell  formation,  or 


Fig.  47. 

Emigration  of  the  leucocytes  in  frog's  mesentery,  six  liours  after  exposure.  Tlio 
cells  shaded  with  lines  are  the  red  corpuscles ;  the  stippled  ones  are  tlie 
leucocytes;    X    2511.      (After  I'erls.) 


whether  certain  granular  changes  of  the  cells  should  be  spoken  of  as 
inflammatory  or  regarded  as  degenerative. 

The  inflammatory  process  ma}^  be  directly  traced  (Cohnheim's 
experiment*)  under  the  microscope  in  transparent  inflamed  living 
tissue,  as  the  mesentery  of  a  frog  or  rabbit,  or  in  the  expanded 
wing  of  a  bat  or  the  tongue  of  a  frog  drawn  out  from  the  mouth 
or  in  the  web  of  a  frog's  foot,  the  inflammation  being  excited  in 
such  tissue  by  the  application  of  a  caustic  or  the  production  of  a 
minute  traumatic  lesion. 

The  first  step  of  inflammation  in  a  vascular  tissue  consists  of 

*For  details  cf.  Kitt.  Baktoirnkinulc  uiul  pathol.  iitlkruskopic  ju>'  Tier'drzte. 
IV    Aufl.    W^en,    M.    Perles    Verlag,    1903. 


262 


Inflammation. 


distension  of  the  blood  vessels,  hypersemia.  In  the  exposed  or  irri- 
tated parts  there  may  be  first  observed  a  dilatation  of  the  arteries 
and  later  of  the  capillaries  and  veins.  With  this  the  blood  current 
is  first  accelerated,  but  with  the  occurrence  of  dilatation  of  the  veins 
of  the  tissue  the  circulation  becomes  slowed.  Here  or  there  it  may 
stop  for  a  variable  period,  and  the  corpuscles  which  previously 
were  forced  along  in  the  central  part  of  the  stream  become  dis- 
tributed uniformly  throughout  the  lumen  of  the  vessel  in  the  stag- 
nating blood.  In  addition  the  delicate  capillaries,  through  which 
previously  plasma  mainly  flowed  with  here  and  there  a  blood  cell, 
are  found  engorged  with  blood  corpuscles.  With  this  slowing  of 
the  current  the  sluggishly  moving  white  blood  cells  tend  to  collect 


A 


a 


■iS-'- 


Fig.   48. 

Various  steps  iu  the  passage  of  a  white  blood  corpuscle  through  the  wall  of  a 
vessel.  On  the  left  of  the  short  lines  which  represent  the  vessel  walls,  is 
supposed  to  be  the  intravascular  blood;  on  the  right  the  tissue;  X  1,0"0. 
(After  Thoma.) 


more  and  more  on  the  inner  surface  of  the  vessel  wall,  giving  rise 
to  the  so-called  marginal  deposition  of  the  white  corpuscles,  and  as 
additional  ones  are  continually  added  from  the  blood  the  capillaries 
may,  from  their  increasing  accumulation,  be  found  completely  oc- 
cluded by  leucocytes.  There  may  next  be  observed  a  very  charac- 
teristic feature,  the  exudation  or  emigration  from  the  vessels  of 
large  numbers  of  the  white  corpuscles  into  the  area  of  inflammation. 
These  motile  amoeboid  cells,  which  were  more  or  less  flattened 
against  the  internal  surface  of  the  vessel,  penetrate  the  capillary  or 
venous  walls  by  protruding  a  pseudopod-like  process  of  their  pro- 
toplasm through  it  (mainly  at  the  cement  lines  between  the  endo- 
thelial cells)   the  rest  of  the  protoplasm  following  in  a  distinctly 


Phenomena  of  JitHainmation. 


263 


flowing  manner  until  the  whole  cell  is  on  the  outside.  In  the  living 
specimen  all  of  the  steps  of  the  passage,  so  like  a  creeping  move- 
ment, ma}'  be  followed ;  and  in  sections  of  an  inflamed  tissue  cells  may 
be  found  partly  outside  and  partly  within  the  vessels,  fixed  in  their 
constricted  condition  and  reminding  one  very  much  of  the  appear- 
ance of  a  wasp  with  its  abdomen  constricted  from  the  thorax.  Some- 
times these  cells  show  a  long  stretched  out  protoplasmic  process, 
swollen  out  into  a  button  in  case  a  part  of  tlie  substance  with  the 
nucleus  has  moved   forward.     The  leucocytes  which  have  escaped 


Fig.  49. 

An  inflammatory  focus   the  seat  of  cellular  infiltration  in   tlie  tissue  of  the  kidney. 

(Section    of    the    kidney   of   a    cat.) 

from  the  vessels  continue  their  creeping  movement  and  thus  dis- 
tribute themselves  in  the  spaces  and  interstices  of  the  tissue  of 
the  inflaminatory  area  between  the  connective  tissue  cells  and  fibril- 
lary bundles,  and  wandering  on  between  the  epithelial  cells  to  the 
free  surface  of  the  part. 

As  new  cells  are  constantly  passing  from  the  vessels  the  inflamed 
tissue  becomes  thickly  studded  with  leucocytes,  constituting  a  con- 
dition known  as  eelhilar  infiltration.'  A  number  of  authors  believe 
that  the  leucocytes  after  their  egress  from  the  vessels  multiply  in 
the  tissues  by  amitosis  (direct  division),  and,  too,  that  the  lymphoid 


264  Inflammation. 

cells  find  their  way  into  the  part  from  the  lymphatic  foci  scattered 
about  in  all  organs. 

Along-  with  the  leucocytes  the  fluid  blood  plasma  also  escapes  in 
greater  or  less  amount  from  the  distended  vessels,  by  a  process  of 
leaking  through  the  walls  through  the  openings  made  by  the  leuco- 
cytes and  directly  through  the  endothelial  cells  which  have  from 
injury  become  more  readily  penetrable;  or,  as  some  maintain,  the 
fluid  is  given  off  to  the  tissues  as  a  secretion  of  the  endothelium. 
It  is  possible  that  red  blood  cells  may  also  escape  from  the  vessels, 
mixed  with  the  fluid,  being  passively  forced  through  any  existing 
openings  by  the  extra  blood  pressure.  The  transuded  blood  plasma 
with  its  celhflar  elements  is  known  briefl\-  as  the  exudate  (from 
e.vsudare,  to  exude). 

The  histological   events  just  detailed  place  us  in  a  position  to 
understand  why  and  how  the  phenomena  spoken  of  as  the  cardinal 
'symptoms  of  inflammation  are  produced. 

The  redness  (rubor)  is  the  result  of  the  hyper?emia.  In  earlv 
stages  of  the  process  and  in  the  peripheral  zone  of  an  inflammatorv 
area,  where  the  blood  current  is  accelerated,  this  hypersemia  has  the 
characteristics  of  an  arterial  hyperjemia,  the  vessels  showing  up 
conspicuously  with  a  scarlet  red  color  as  if  injected  (injection  red- 
ness, branched  redness).  The  more  pronounced  the  slowing  of  the 
current  and  the  more  the  stagnating  blood  gives  off  its  oxygen  to  the 
inflamed  tissue  the  more  the  color  approximates  that  of  the  venous 
blood,  becoming  darker  and  of  a  more  violet  hue  and  becoming 
more  and  more  dift'use  as  the  dilatation  of  all  the  capillaries  de- 
velops. The  heat  (calor)  depends  upon  the  increased  rapidity  of 
flow  and  the  volume  of  arterial  blood;  the  more  rapid  the  current, 
the  less  opportunity  being  aft'orded  for  loss  of  heat  and  the  more 
nearly  the  temperature  of  the  inflamed  part  approximates  the  tem- 
perature of  the  blood  itself.  The  heat  of  an  inflamed  area  is  only 
noticeable  on  the  exterior  of  the  body,  in  comparison  with  the  parts 
whose  temperature  is  unchanged,  and  is  not  above  the  temperature 
of  the  general  blood.  The  internal  organs  do  not  become  essentially 
warmer  than  the  blood,  special  increase  of  temperature  from  meta- 
bolic changes  not  taking  place  in  inflamed  parts  (Perls,  Ribbert). 
[It  is  claimed  by  some,  however,  on  the  basis  of  experiments  carried 
on  it  is  true  with  difficulty  and  open  therefore  to  a  chance  of  error, 
that  the  blood  coming  from  an  inflamed  part  is  of  higher  tempera- 
ture than  that  of  the  arterial  blood  going  to  such  a  part,  and  that 
increase  of  temperature  is  actually,  therefore,  produced  in  inflamma- 
tion   presumably    from    an    increased    metaboUsm    which    obtains.] 


Signs  of  IiiflaDiiiHition.  265 

The  szi'dliiig  (tumor)  of  an  inflamed  tissue  is  easily  comprehended. 
The  exudate  fills  up  the  lymph  spaces  and  stretches  the  structures 
apart ;  the  vessels  are  dilated,  and  the  lymph  is  prevented  from  es- 
caping readily  from  the  tissue  because  of  loss  of  elasticity  of  the 
interstitial  substance  (Landerer).  In  consequence  a  turgescence, 
appreciable  as  an  oedematous  swelling  in  inflamed  areas  on  the 
periphery  of  the  body,  occurs.  In  chronic  inflammations  the  con- 
nective tissue  proliferation  gives  to  the  organ  or  its  connective 
tissue  frame-work  more  or  less  increase  of  volume.  The  pain 
(dolor)  is  attributable  to  the  pressure  exerted  by  the  exudate  and 
swollen  tissue  upon  the  sensory  nerve  filaments,  or  to  direct  irrita- 
tion of  the  latter.  In  addition  this  fault  interferes  with  the  trans- 
mission of  nervous  impulses,  in  consequence  of  which  arises 
functional  disturbance,  in  addition  to  the  disturbance  occasioned  by 
the  primary  influence  of  the  cause  of  the  inflammation  (death  of 
tissue)  and  the  simple  mechanical  disturbances  produced  by  the 
collection  of  exudate  in  cavities  (as  the  air  spaces  of  the  lung  or 
the  pleural  cavities),  the  overgrowth  of  tissue,  etc. 

As  already  stated,  the  processes  involved  in  inflammation  are 
nothing  but  modifications  of  physiological  processes.  Exudation  of 
plasma  and  leucocytes  and  their  movement  through  the  tissues  are 
continuallv  going  on  under  normal  conditions ;  the  ordinary  lymph 
formation  is  the  result  of  a  normal  process  which  in  inflammation 
is  clearlv  only  exaggerated.  The  reason  for  this  heterometria. 
and  more  particularly  for  the  circulatory  disturbances,  may  be  found 
in  certain  physical  and  chemical  changes  in  the  vessel  wall.  All 
inflammatory  excitants  apparently  exert,  directly  or  indirectly, 
chemical  influences  leading  to  changes  of  the  endothelium  of  the 
vessels  and  thus  making  the  vessel  wall  more  permeable  than  nor- 
mally. It  can  be  shown  for  example  that  the  endothelial  cells  may 
be  caused  to  shrink,  contract  into  spherical  form,  and  thus  give  rise 
to  imperfections  in  their  interstitial  cement.  These  openings  pro- 
duced pathologically  facilitate  the  leakage  of  the  plasma  and  the 
emigration  of  the  leucocytes  through  the  wall  and  make  it  possible 
for  the  red  cells  to  undergo  diapedesis.  Changes  in  the  tension 
of  the  vascular  wall,  relaxation  of  the  arterial  musculature,  neces- 
sarily accompany  lesions  of  the  endothelial  cells  and  the  surrounding 
tissues,  and  this  in  turn  occasions  dilatation  of  the  vessels.  In  every 
case,  too,  the  nervous  system,  especially  the  network  of  vasodilators 
and  vasoconstrictors  distributed  about  the  vessels,  takes  part  in 
bringing  about  the  vascular  dilatation,  these  nerves  being  affected, 
irritatecl  or  paralyzed,  by  the  original  cause  of  the  inflammation. 


266  Inflammation. 

The  acceleration  of  the  blood  current  which  is  seen  in  the  early 
stages  depends  on  the  passage  of  the  blood  from  narrow  into  wider 
channels  [an  explanation  sufficient  for  the  short  period  required  for 
the  filling  of  the  additional  space  afforded  by  the  dilated  lumen  of 
the  vessel,  but  not  clearly  satisfying  for  its  continuation  even  for  the 
time  it  does  prevail  before  stasis  sets  in,  and  for  its  longer  persist- 
ence at  the  periphery  of  the  inflamed  area]  ;  the  slowing  of 
the  current  upon  the  transudation  of  the  plasma,  and  the  endothelial 
changes,  both  of  which  tend  to  cause  a  more  concentrated  condition 
of  the  blood.  [Here,  too,  there  should  be  considered  the  probability 
of  relative  inefficience  in  the  outflow  of  the  blood,  loss  of  tone  of 
the  venous  walls  and  loss  of  elasticity  of  the  surrounding  tissues, 
local  compression  of  the  walls  of  the  capillaries  and  venules  by  exu- 
date and  proliferating  or  swollen  and  degenerate  cells,  all  of  which 
introduce  elements  of  a  relatively  passive  factor  in  the  process  for 
retardation  of  the  escaping  current.]  The  marginal  deposition 
of  the  white  corpuscles  is  explained  by  Hering  and  Schklarewski  by 
the  fact  that  when  liquids  containing  light  bodies  in  suspension  are 
passed  through  tubes  these  bodies  tend  to  move  along  the  periphery 
as  the  rapidity  of  the  current  is  slowed ;  they  call  attention  to  the 
lower  specific  gravity  of  the  white  in  comparison  with  the  red  cells 
and  their  viscidity  and  tendency  to  adhere  from  their  tactile  irri- 
tability. The  movement  of  these  cells,  physiologically  determined 
everywhere  by  their  tactile  and  chemotactic  sensibility,  is  stimu- 
lated in  inflamed  tissues  both  by  the  causes  of  the  inflammation 
and  by  the  lesions  occasioned  by  these  causes.  The  studies  of 
Pfefifer,  Buchner  and  others  have  made  us  acquainted  with  a  series 
of  substances  which  possess  marked  power  of  attraction  for  leu- 
coc>'tes,  especially  certain  proteins  of  the  bacterial  body ;  and  in  the 
destruction  of  tissue  induced  as  a  primary  effect  of  the  untoward, 
influences  exerted  by  the  causes  of  inflammation  certain  chemical 
substances,  as  the  alkali  albuminates,  are  set  free  which  have  a  sim- 
ilar attractive  influence  upon  the  leucoc>i:es.  According  to  Thoma, 
even  a  variation  in  the  amount  of  saline  matter  in  a  tissue  will 
occasion  a  movement  of  the  leucocytes. 

The  spaces  produced  between  the  endothelial  cells  are  appar- 
ently not  primarily  due  to  perforative  efforts  by  the  leucocytes,  but 
result  from  distension  of  the  vessel  or  from  shrinkage  of  the  endo- 
thelial cells ;  and  the  leucocytes  possessing  tactile  sensibility,  closely 
adapting  their  substance  to  the  surface  and  fitting  into  every  varia- 
tion,  extend  their  processes,   tentatively   and   uncertainly,   through 


Exudate  and  Proliferate.  267 

any  existing  openings.  The  presence  of  any  substance  with  chemo- 
tactic  power  determines  the  direction  taken  in  the  further  move- 
ments of  these  cells. 

The  majority  (about  seventy  per  cent.)  of  the  motile  cells  col- 
lectively spoken   of  as  leucocytes,  which   are   found  in  an  infiam- 
matory   focus,   are  characterized    by    the    possession    of    multiple 
nuclei,  or  one  polymorphous  nucleus,  and  very  fine  granulations  only 
seen  in  fresh  specimens.     These  polymorphonuclear  forms  are  re- 
garded as  the  characteristic  white  blood  cells  and  arise  from  the 
bone  marrow   (where  they  are  mononuclear,  acquiring  biscuit  and 
clover  leaf  types  of  nuclei  only  in  passing  into  the  blood  as  the 
result  of  nuclear  division  or  fragmentation).     Besides  these,  which 
are  described  by  Ehrlich  as  neutrophilic  leucocytes,  there  are  met 
in  inflamed  tissues   forms  containing  coarser  granules  which,   be- 
cause of  the  readiness  of  their  granules  to  take  up  intensely  'the 
acid  aniline  dyes,  like  eosin,  are  known  as  eosinophile  leucocytes; 
and  others  with  special  tinctorial  tendency  of  their  coarse  granules 
for   the   alkaline    anilines    (gentian   violet),   known   as   mast   cells. 
Mononuclear  (single  nucleus)  cells  are  also  comparatively  numer- 
ous in  inflamed  tissue,   the  nucleus  round  and  rich  in  chromatin, 
and  the  cytoplasm  showing  as  a  very  narrow  margin  about  the 
small  or  large  nucleus.    These  are  regarded  as  lymphocytes,  which 
have    originated    from    the    lymph    glands    or    germinal    lymphatic 
centres.     As   above   mentioned,   the   great   increase   of  these   cells 
depends  in  part  upon  a  chemical  stimulation  acting  not  only  on  the 
blood  vessel  walls  but  also  upon  the  foci  of  lymphoid  cells   dis- 
tributed in  all  the  tissues  and  causing  enlargement  of  these  lymph- 
cell  forming  centres;  and  in  the  second  place,  as  many  of  these 
cells  have  come  from  the  marrow,  it  may  be  inferred  that  these 
chemical  substances,  which  act  locally  in  the  inflammatory  area  as 
chemotactic  agents  and  stimulants  to  proliferation,  are  also  present 
in  the  circulating  blood  and  with  it  pass  into  the  bone  marrow  and 
there  exert  the  same  influence,  that  is,  stimulate  this  tissue  to  the 
formation  of  leucocytes.     Often  in  inflammation  there  is  not  only  a 
swelling  of  the  lymph   follicles,  but  even  a  hyperplasia  or   meta- 
plasia (change  of  red  marrow  into  lymphoid)  of  the  bone  marrow 
referable  to  its  exaggerated  function. 

The  causes  of  inflammation  and  the  chemotactic  substances  set 
free  in  the  affected  tissue  have,  moreover,  a  stimulating  influence 
upon  the  proliferation  of  the  fixed  eells.  The  endothelial  cells  of 
the  blood  vessels  and  lymphatics  and  the  connective  tissue  cells 
take  part  in  the  proliferation  in  every  inflammation,  the  beginning 


268 


tnflmnmation. 


of  proliferation  being  indicated  by  the  appearance  of  mitotic 
changes.  After  conclusion  of  mitosis  the  cellular  division  takes 
place,  the  protoplasm  also  increasing  in  volume.  The  young  cells 
arising  from  this  proliferation  persist  in  part  in  the  inflamed  tissue, 
and  after  the  formation  of  an  intercellular  substance  constitute  an 
inflanuuatory  embryonic  tissue,  made  up  of  fibroblasts  and  angio- 
plasts,  which  serves  the  purpose  of  restoration  of  the  original  lesion 
(cf.  Regeneration,  p.  237).  In  part  these  cells  disappear,  and  they 
may  perhaps  exhibit  motile  activity.     A  number  of  the  proliferating 


Fig.   50. 
Inflammatory    focus    in    kidrey    of    calf,    sliowing    cellular    infiltration. 

connective  tissue  cells  and  endothelial  cells  are  sometimes  changed 
by  direct  nuclear  division  into  multi-nucleated  giant  cells.  The  forma- 
tion of  these  giant  cells  is  by  some  supposed  to  be  due  to  a  chemo- 
tactic  influence  bringing  a  number  of  cells  together  and  causing 
their  fusion ;  another  suggestion  is  that  the  cause  of  the  inflam- 
matory change  has  in  some  way  disturbed  the  protoplasm  of  a  cell 
so  as  to  interfere  with  division  of  the  cell  substance,  although 
nuclear  division  goes  on.  This  type  of  cell  is  met  especially  in 
inflammation  excited  by  foreign  bodies,  about  which  corpuscular 
elements  the  giant  cells  are  found  deposited  in  a  manner  explain- 


Demarcation  and  Phagocytosis. 


269 


ing  how  the  inflammatory  reaction  is  able  to  carry  out  its  protec- 
tive purpose  by  removal  or  encapsulation  of  the  harmful  substances. 
Demarcation  and  Phagocytosis  are  two  important  functions  of 
the  cells  coming  into  consideration  in  the  inflammatory  process. 
The  motile  cells  of  leucocytic  and  lymphoid  types,  distinguished 
generally  for  their  phagocytic  properties  even  in  normal  circum- 
stances, arc  attracted  by  the  metabolic  products  of  an  injured  tis- 
sue or  bv  the  chemical  influences  of  the  inflammatory  agents.  They 
take  u])  all  the  substances  in  a  disintegrating  tissue  which  are  acces- 


Fig.    51. 
Inflammatory  scar  in  the  kidney   of  a   hug. 

sible  and  with  which  they  can  deal,  as  albuminous  granules,  blood 
remnants,  pigmentary  granules  and  fat  globules,  and,  indeed,  all 
sorts  of  minute  particulate  elements,  as  vegetable  and  animal  micro- 
organisms ;  carrying  these  objects  off  or  destroying  and  rendering 
them  inert  by  the  influence  of  the  digestive  power  of  their  proto- 
plasm. However,  this  power  of  phagocytosis  also  resides  in  the 
fixed  cells.  In  the  chemotactic  accumulation  of  the  cells,  which 
takes  place  around  foreign  bodies  or  necrosed  tissue,  the  leucocy- 
tes, fibroblasts  and  angioplasts  and  giant  cells  form  a  protective 
wall  which  either  permanently  imprisons  the  foreign  body  or  from. 


270  '  Inflammation. 

which  fresh  cells  constantly  move  into  the  dead  structure,  grow 
all  through  it  and  break  it  down,  bearing  away  particles  of  the 
disintegrated  material  or  any  minute  foreign  elements  (bacteria, 
etc.),  and  in  this  way  gradually  removing  tlie  agents  producing  the 
inflammation. 

These  features  have  been  studied  experimentally  in  a  variety 
of  ways.  They  may  be  easily  observed  by  injecting  into  a  tissue 
an  emulsion  containing  fine  particles  of  carmine.  An  inflamma- 
tion is  determined  in  the  course  of  which  the  leucocytes  and  fibro- 
blasts become  loaded  with  pigment  granules,  and  giant  cells  are 
formed  which  also  englobe  the  pigment  particles.  Some  of  the 
carmine  is  carried  out  of  the  area  by  the  motile  cells ;  when  larger 
amounts  have  been  introduced  tlie  parts  which  cannot  be  carried 
away  are  encapsulated  by  the  connective  tissue  cells  and  the  cica- 
tricial tissue  arising  from  the  latter.  When  porous  foreign  bodies 
like  bits  of  sponge  or  elder  pith  are  introduced  aseptically  into  the 
subcutaneous  tissue  or  into  the  peritoneum,  at  first  the  exuding 
plasma  and  a  large  number  of  leucocytes  occupy  the  spaces  in  the 
substance,  but  later  the  connective  tissue  corpuscles  and  vascular 
buds  penetrate  into  them  and  take  up  all  the  available  space  (this 
reactive  proliferation  is  seen  as  early  as  the  second  day). 

After  transformation  into  scar  tissue  (v.  p.  241)  the  connective 
tissue  is  found  surrounding  and  filling  all  tlie  spaces  of  the  foreign 
substance  and  isolating  it  from  the  rest  of  the  organism  (Ribbert). 
Solid  foreign  material  like  silk  thread,  cat  gut,  silver  wire,  intro- 
duced aseptically  as  sutures  by  surgeons,  or  bullets,  needles,  bits  of 
glass,  w^ood  splinters,  or  hairs  which  have  gotten  into  wounds,  pro- 
vided they  have  no  bacteria  upon  them  and  are  truly  aseptic  for- 
eign bodies  in  the  tissue,  are  always  surrounded  by  a  wall  of  leu- 
cocytes and  proliferating  connective  tissue  and  thus  encapsulated. 

The  inflammatory  reaction  about  a  foreign  body  always  depends 
upon  the  soluble  chemotactic  substances  which  arise  from  the  mate- 
rial. About  some  bodies  which  give  rise  to  but  little  substance  of 
this  sort  (aseptic  cat-gut,  silver  wire)  it  may  be  very  unimportant; 
inflammation  ceases  entirely  after  these  substances  are  completely 
extracted  from  the  foreign  body,  that  is  when  it  can  no  longer 
give  ofif  soluble  chemotactic  material.  The  functional  activity  and 
the  movement  of  the  cells  mentioned  toward  the  foreign  matter  can 
be  beautifully  demonstrated,  as  pointed  out  by  Ribbert.  by  inject- 
ing liquefied  agar  or  a  blue-stained  mass  of  gelatin  into  the  sub- 
cutaneous tissue  or  anterior  chamber  of  the  eye.  Soon  after  the 
jelly  has  hardened  in  the  body  it  is  surrounded  by  leucocytes  and 


Iniiamiuatioii  in  Non-Vascular  Parts.  271 

fibroblasts  which  approach;  these  cells  push  forward  and  into  the 
jelly  like  a  phalanx  of  soldiery,  break  it  down  and  gradually  carry 
it  entirely  away;  and  the  local  inflammatory  condition  disappears 
with  the  removal  of  the  foreign  matter,  the  leucocytes  and  other 
cells  being  able  to  return  whence  tliey  came,  or  some  perhaps  dying 
and  undergoing  disintegration. 

Hc-emorrhagic  effusions,  blood  clots,  masses  of  fibrin,  coagu- 
lated or  completely  necrosed  tissue  and  loose  bits  of  bone  are  all  in 
the  same  way  objects  for  phagocytic  activity  of  the  cells,  making 
their  appearance  in  the  tissue  reactions  in  inflammation.  All  dead 
tissue,  in  fact,  is  the  same  thing  as  a  foreign  body  in  relation  to 
the  functionating  living  tissue  adjacent  to  it;  it  is  a  source  of 
chemotactic  substances  and  acts  as  an  excitant  of  inflammation.  So, 
too,  just  as  non-vital  foreign  bodies,  the  living  organisms  which 
enter  the  body  from  the  exterior,  the  animal  parasites  and  all 
microbes,  are  to  be  looked  upon  as  irritants  and  as  causative  of 
inflammation  to  a  greater  or  less  degree,  according  to  the  chemo- 
tactic substances  which  they  contain. 

Inflammation  in  non-vascular  parts  of  the  body,  of  which  there 
are  two  which  require  special  mention,  the  cornea  and  the  cardiac 
valves  (cartilage  and  the  calcified  bone  substance,  which  are  also 
avascular,  have  no  marked  inflammatory  reactive  power  and  are 
subject  merely  to  retrograde  metamorphoses),  presents  practically 
the  same  features  as  in  the  vascular  tissues,  save  that  emigration 
and  exudation  of  course  cannot  take  place  where  there  are  no  ves- 
sels, but  do  occur  from  vessels  at  a  distance.  Numerous  investi- 
gators, particularly  His  and  Virchow,  and  besides  these  Cohnheim, 
Fuchs,  Eberth.  Ranvier,  Giiterbock.  Ribbert  and  Marchand,  have 
engaged  in  studies  in  connection  with  the  process  in  question,  and 
have  thereby  materially  added  to  our  appreciation  of  the  nature  of 
inflammation.  Where  the  cornea  has  been  injured  by  some  trau- 
matic lesion,  by  a  foreign  body,  or  some  type  of  infection,  leuco- 
cytes actively  penetrate  to  the  focus  from  the  blood  vessels  which 
encircle  the  margin  of  the  cornea  in  the  conjunctiva.  Although 
these  vessels  are  situated  some  distance  from  the  focus  of  injury 
there  are  to  be  noted  in  them  the  same  dilatation,  slowing  of  the 
current  and  emigration  as  if  they  were  immediately  in  the  injured 
area.  It  is  probable  that  these  vessels  are  influenced  by  reflex  ner- 
vous action,  and  it  cannot  be  doubted  that  the  injured  corneal  tissue 
exerts  a  strong  chemical  attraction  for  the  leucocytes  by  means  of 
substances  dissolved  in  the  corneal  lymph  and  reaching  the  corneal 
margin   in   the  latter  or  exerting    a    far-reaching    influence    from 


2^2  Inflammation. 

within  tlie  corneal  mass.  The  leucocytes  which  escape  from  the 
blooci  vessels  at  the  corneal  border  find  their  way  along  the  spaces 
of  the  corneal  tissue  to  the  point  of  injury  and  there  collect  about 
it.  This  can  be  observed  in  the  frog's  cornea  which  has  been 
touched  with  a  corrosive,  if  the  animal  be  killed  a  day  or  two  later 
and  the  excised  cornea  spread  out  on  a  glass  slide,  as  the  leucocytes 
of  this  cold-blooded  animal  retain  tlieir  motility  for  a  considerable 
time.  The  wandering  cells  are  found  elongated  and  conforming 
in  shape  to  the  narrow  tissue  spaces,  their  presence  giving  the  cor- 
nea a  milky  cloudiness.  At  the  same  time  the  corneal  cells  are 
found  proliferating;  they  undergo  division  and  become  slightly 
motile  in  response  to  the  chemotactic  agent  connected  with  the 
inflammation.  If  the  inflammation  continue  for  a  comparatively 
long  time,  eventually  the  marginal  vessels  begin  to  send  vascular 
buds  into  the  cornea ;  these  may  penetrate  so  far  that  the  cornea 
becomes  covered  or  completely  penetrated  by  a  network  of  vessels, 
a  pannus  ( •v  tti^j/tj,  a  cloth).  This  proliferation  is  also,  according 
to  Ribbert,  probably  due  to  a  chemotactic  stimulus  affecting  the 
endothelial  cells.  The  opacity  which  involves  the  cornea  in  the 
course  of  the  process  mentioned  may  entirely  disappear  with  the 
completion  of  repair;  the  transparency  returns  because  the  cells 
creep  back  and  the  fluid  washes  out  the  products  of  disintegration 
and  the  capillaries  undergo  regressive  changes.  In  other  cases  a 
whitish  scar  remains  as  a  remnant  of  the  proliferated  tissue. 

Inflammation  of  the  cardiac  z'ah'cs,  according  to  Ribbert,  is  not 
attended  by  penetration  of  leucocytes  into  the  tissue  at  all ;  aside 
from  the  formation  of  adhesive  clots,  which  develop  upon  the 
roughened  (from  endothelial  lesion)  leaflet,  the  only  evidence  of 
reaction  consists  in  a  multiplication  of  the  fixed  cells  of  the  endo- 
cardium and,  in  case  the  process  continue  for  a  time,  of  the  pene- 
tration of  the  capillary  vessels  from  the  base  of  the  valve  into  its 
substance. 

Anatomical  Types  of  Inflammation  and  Exudation. — lExudation 
of  blood  plasma,  emigration  of  leucocytes  and  sometimes  diapedesis 
of  red  cells  occur  in  varying  degree,  depending  upon  the  causes  of 
the  inflammation,  its  duration  and  local  conditions ;  and  give  rise 
to  special  appearances  which  form  the  basis  for  differentiating  a 
number  of  forms  of  inflammation  and  exudate. 

The  volume  of  exudate  varies  within  wide  limits ;  it  may  be  so 
small  that  the  inflammatory  focus  can  be  found  practically  only 
with  the  aid  of  the  microscope,  or  there  may  be  such  a  quantity  of 
fluid  that  many  liters  may  be  removed  (from  the  larger  cavities  of 


Serous  and  Fibrinous  liifhuiiinatious.  273 

the  body).  The  exudate  may  exist  in  the  lymph  spaces  of  the  tissues, 
fining  them  completely  (infiltration),  or  may  escape  to  the  surfaces, 
where  it  forms  a  deposit  upon  the  latter ;  it  may  collect  in  the  body 
cavities  or  may  find  free  exit  from  the  body.  Even  in  normal  con- 
ditions leucocytes  find  their  way  between  epithelial  cells,  and  when 
the  epithelial  tissues  are  loosened  in  inflammation  or  actually  des- 
quamated the  exudate  is  given  easy  access  to  the  free  surface.  The 
qualitative  composition  of  the  exudate  is  by  no  means  uniform ; 
sometimes  the  major  portion  is  plasma  and  cells  are  but  scantily 
met  in  it,  sometimes  the  reverse  is  true.  In  addition  admixtures  of 
tlie  secretions  of  organs  may  be  found  present,  or  products  of  tis- 
sue disintegration  or  changes  due  to  coagulation,  putrefaction  or 
inspissation.  all  of  which  serve  to  give  a  very  variable  character  to 
the  exudation. 

The  terms  serous  exudate  and  serous  inflammation  are  employed 
in  connection  with  an  aqueous  product  of  inflammatory  extravasa- 
tion :  the  fluid  is  rich  in  albumen,  like  the  serum  of  the  blood,  lim- 
pid or  slightly  clouded,  of  a  yellow  wine  tint,  or  sometimes  red 
from  the  presence  of  erythrocytes.  When  it  soaks  through  a  tissue- 
and  gives  it  a  juicy  gelatinous  appearance  the  structure  is  said  to  be 
the  seat  of  iiif^aiiiinatory  a^ieuia;  collecting  in  the  sacs  of  joints, 
tendon  sheaths  and  the  serous  cavities  the  expression  inflammatory 
dropsx  is  applied.  In  the  skin  surfaces,  which  are  covered  with 
squamous  epithelium,  the  upper  layers  of  which  are  but  slightly 
permeable  for  fluids,  it  may  collect  in  the  more  easily  penetrated 
deeper  layers  of  the  rete  ]\Ialpighii  and  raise  up  the  superior  strata 
to  the  formation  of  blisters.  In  mucous  membranes  the  fluid  passes 
through  the  epithelial  layer  and  mingles  with  the  physiological  secre- 
tion and  the  desquamated  cells  of  the  membrane,  escaping  with 
these ;  in  this  case  the  term  catarrhal  exudate  (Karap^o}.  to  flow 
away)  is  employed.  Such  catarrhal  exudate  may  be  very  thin  and 
water  like,  or  may  be  viscid.  The  irritation  of  the  inflammatory 
condition  invariably  induces  an  increase  of  secretion  (increased  flow 
of  tears,  increased  secretion  of  nasal  mucus). 

It  is  said  to  be  a  fibrinous  exudate  in  case  the  exuded  fluid  under- 
goes coagulation  by  precipitation  of  fibrin.  This  form  is  met  par- 
ticularly on  the  free  surfaces  of  serous  membranes  and  mucous 
membranes,  within  joints  and  in  the  lung,  and  to  a  less  degree  in 
the  meshes  of  the  tissue.  Coagulation  occurs  in  case  the  fibrin 
forming  substance,  which  is  always  abundantly  present  in  every 
exudate,  comes  in  contact  with  fibrin  ferment,  the  latter  being  sup- 
plied by  necrosing  cells,  especially  leucocytes  and  endothelial  cells. 


274 


Inflammation. 


The  fibrinous  exudate  may  form  delicate  or  thick,  more  or.  less  ad- 
herent, grayish  white  to  yellow  deposits  or  flocculent  precipitates 
of  a  semi-transparent,  elastic  type.  On  the  surfaces  of  serous  mem- 
branes it  may  be  observed  as  a  frost-like  deposit  of  thick  patches 
of  coagulated  substance  which  can  be  torn  off  in  shreds,  look  some- 
thing like  omelet  and  perhaps  cover  considerable  areas  of  the 
serous  surface  (false  membrane).  The  viscidity  of  the  exudate  is 
responsible  for  the  fact  that  on  opposed  surfaces  which  move  over 


«&'iL 


Fig.  52. 
Fibrinous  exudate  on  surface  of  heart  of  tow   (traumatic  pericarditis). 

each  other  (pleura,  diaphragm,  peritoneum)  the  layers  of  exudate 
in  rubbing  upon  each  other  leave  the  fibrinous  material  stretched 
and  dragged  into  a  reticular,  villous  appearance,  reminding  one  of 
butter  on  two  pieces  of  bread  which  have  been  pressed  together 
and  then  pulled  apart,  or  of  the  ridged  appearance  of  tripe  {dry  ox 
fibrinous  e.viidation) .  In  other  instances  the  coagula  of  fibrin  are 
so  large  as  to  appear  as  elastic  rind-like  layers,  thick  as  one's  hand, 
riddled  with  tiny  holes  which  contain  serum ;  or  the  serous  exudate 


Fibrinous  I n/Janinuitioiis.  275 

may  predominate  and  flakes  of  fibrin  be  found  floating  in  it,  in  a 
state  of  fine  division  (sero-fibrinous  exudation).  On  the  mucous 
membranes  also  the  fibrin  may  be  encountered  as  membranous  lay- 
ers, which  may  be  pulled  ofif  in  sticky  shreds,  and  which  sometimes 
form  distinct  casts  of  the  canal ;  these  are  spoken  of  usually  as 
croupous  exudates  (according-  to  Roth  tlie  word  croupous  has  a 
Scottish  origin).  Croupous  membranes  may  be  tough  or  soft  and 
grumous,  depending  upon  the  proportionate  number  of  cells  present 


■% 


V 


Fig.  53. 

Enteritis  membranacea  of  cat  (section).  To  tlie  left  tlie  pseiirlomembrane  cover- 
ing the  intestinal  villi,  wliicli  are  the  seat  of  cellular  infiltration  and  des- 
(inamation ;  to  the  right  the  muscular  layers  and  the  serosa  with  its  adipose 
tissue. 

and  the  existence  of  some  degree  of  degeneration ;  they  vary  from 
one-half  to  ten  millimeters  in  thickness ;  when  separated  in  the  form 
of  tubes  they  are  full  of  the  contents  of  the  mucous  canal,  as  the 
intestine,  in  which  they  develop ;  in  other  instances,  as  in  the  lungs, 
they  form  solid  coagula.  Under  the  microscope,  at  the  beginning 
of  fibrin  separation  the  fibrin  threads  can  often  be  seen  arranged  in 
a  stellate,  tuft-like  manner  about  the  cells  which  give  origin  to  the 
fibrin  ferment  (Hauser)  ;  sometimes  the  fibrillar  material  is  depos- 
ited in  parallel  layers  or  is  formed  in  a  reticulum,  the  meshes  of 


2y(i 


Inflammation. 


which  are  occupied  by  leucocytes,  desquamated  epitheUum  and 
serum.  By  the  cohesion  of  the  fibrin,  originally  separated  in  the 
form  of  fine  fibrils,  thick  homogeneous  trabecula  are  sometimes  pro- 
duced (hyaline  fibrin). 

Fibrin  may  be  well  demonstrated  in 
microscopic  sections  by  Weigert's  double 
staining  method,  the  fibrin  taking  an  in- 
tense blue  tint,  and  the  rest  of  the  tissue 
a  red  contrast  color. 

Inflammations  of  mucous  mem- 
branes, in  which  in  addition  to  the 
formation  of  a  fibrinous  exudate  there 
takes  place  a  coagulation  necrosis  of 
the  tissue  of  the  mucous  membrane, 
are  spoken  of  as  diphtheritic  inflam- 
inations  {5i<t>eipa,  membrane).  The 
coagulation-necrotic  mass  is  here 
seen  as  a  grayish-yellow  to  straw- 
colored  or  dirty  gray,  soft  and  pulta- 
ceous  or  drier,  very  opaque  and  usu- 
ally fragmented  material.  which 
stands  out  sharply  from  the  slightly 
transparent  normal  tissues  as  a 
thicker,  somewhat  swollen,  promi- 
nent part.  Here  the  deeper  parts  of 
the  mucous  membrane  are  permeated 
with  the  exudate,  and  the  substance 
cannot  be  as  readily  separated  from 
the  underlying  tissue  as  the  ordinary 
croupous  exudate,  the  mucous  mem- 
brane being  torn  when  attempts  are 
made  to   scrape   it  away. 

This    combined   inflammation   and 
p.     g^  necrosis  in  its  typical  form  is  met  in 

Croupous    membrane    in    trachea      the   digestive  tract  of  swine  afifccted 
(opened)  of  cow.  ^^..^j^  ^^^^.^^  ^\?igix^,  and  is  oftcn  Seen 

in  calves  in  the  pharynx  and  larynx  following  traumatic 
infectious  influences,  in  birds  in  the  mucous  membranes  of 
the  head,  and  in  horses  in  the  larynx  and  trachea  after  drenching. 
There  are  a  number  of  microorganisms  (bacillus  necrophorus, 
suipestifer,  streptococci  and  others)  which  are  capable  of  inducing 
coagulation  necrosis  of  tissues  and  giving  rise  to  the  anatomical 
picture  of  a  diphtheroid  inflammation.^ 


Suppurative  Infiamviation. 


277 


(In  man  the  name  diphtheria  is  applied  to  a  specific  infectious  disease 
caused  by  bacillus  diphthcrice,  usually  accompanied  by  deeply  penetrating 
fibrinous  inflamnialion  of  the  pharyngeal  mucous  membrane.  Anatomically 
similar  conditions,  due,  however,  to  other  causative  agents,  are  spoken  of 
as  diphtheroid,  to  distinguish  them  from  true  diphtheria.  This  name 
diphtheria  has  not  been  happily  chosen,  however,  as  it  really  means  inflam- 
mation   of    the    membrane.) 

Suppurative  InflammatioH  with  its  product  pus  (Latin,  pus; 
Greek,  rb  niov)  is  characterized  by  the  hquefaction  of  the  exudate 
and  inflamed  tissue  (purulent  softening)  and  by  the  important  pres- 
ence in  the  exudate  of  fatty  degenerating-  leucocytes  which  have  lost 
their  power  of  movement ;  in  addition  it  is  always  the  result  of  in- 
fection with  microorganisms  known  collectively  as  the  pyogenic 
bacteria  (pus  bacteria).  There  are  a  number  of  these  microorgan- 
isms occurring  free  in  nature,  mainly  belonging  to  the  groups  of 
staphylococci,  streptococci  and  colon  bacilli,  which  are  liable  to  gain 
access  to  the  tissues  through  traumatic  lesions  or  which  may  even 
penetrate  from  the  unbroken  surface  through  the  pores  of  the  skin 


Fig.  .:.r>.  # 

Small    intestine    (laid    opeu)    of    liog    showing    diphtheritic    inflammation    in    swine 

plague. 

or  through  lymph  follicles.  In  addition  to  these  specific  pyogenic 
bacteria,  whose  most  important  influence  is  the  production  of  pus, 
there  are  many  other  microphytes  which  are  also  capable  of  induc- 
ing suppuration,  but  which,  because  of  special  peculiarities  of  their 
toxic  properties  and  the  peculiarities  of  the  diseases  which  they 
cause,  receive  special  names,  as  the  glanders  bacillus,  bacterium  of 
chicken  cholera,  and  actinomyces.  Wherever  suppuration  occurs  in 
a  part  an  infection  is  to  be  suspected.  This  statement,  first  empha- 
sized by  Lister  and  Hunter,  and  of  the  utmost  importance  in  sur- 
gery, is  not  impaired  by  the  fact  that  suppuration  may  be  artificially 
produced  in  experimental  manner  without  the  aid  of  bacteria  by 
means  of  aseptic  chemicals  as  by  subcutaneous  injection  of  turpen- 
tine, croton  oil,  chloride  of  zinc  or  corrosive  sublimate,  under  con- 
ditions which  thoroughly  exclude  the  possibility  of  infection.  Such 
an  aseptic  suppuration  occurs  under  natural  conditions  only  in  the 
rarest  instances,  and  dififers  from  the  ordinary  bacterial  suppuration 


2^  Im&immtHi/tiom. 

m  its  (ddfiaaite  local  Himaitatoooi.  Bacterial  suppaisi^on.  is  progressive 
aaad  as  aoDOnaii^aaaied  by  a  naacsre  or  less  serere  f ■dmle  geaeral  reac- 
tkm  (om  itioe  paat  of  tbiae  solsject. 

As  it  as  ©gimaMy  pos^Me  to  abtain  a  snjjpEuatiTe  inflammaticm  by 
aaoeasss  ©ff  sterille  germ-free  cnltiarts  of  t2ie  p^-ogenic  organisms  or 
fillltinates  wMda  coanain  goiIt  "fee  metabolic  pnodocts  of  the  bacteria, 
at  aaaay  tie  ac"'^*"-'!  tbsl  l3ae  pjog-eaoic  actioai  of  bacteria  is  anotiier 

mstottKne  ©f  _-.- al  acbTit}-;  am  important  factor,  hovre^-er,  being 

ifflne  pjreseare  ©f  ititese  Irving  organisms  wMd3  nraltiply  in  the  tissue. 
Hae  coaac^ati'GBoi  ©f  smpfraratioaii  is  tibeT«f ore  aaa  setiological  one.  The 
j(y©geaaac  csqgaaaisms  exert,  aiaparenitlT  by  -mpaais  of  tjaeir  toxines 
mlnada  aaie  •(Si&ised  tiiTongli  the  lissnes,  an  exfcremelj-  strong  diemo- 
tadtic  srtimnkis  mpom  dae  lencocites  and  in  tbis  ysrsy  indiace  a  greatl}- 
hacres.S'ed  emigiatiom  of  ttliese  c^Hs:  at  the  ^mte  time  they  have  an 
WE^mtaM.  Iianiimfiiall  irnfliaejaoe  tipon  the  -sralls  of  the  vessels  and  nerves, 

IS  camsimg  Ih3"]j>eTaBmia  aaad  voluminoiis  exudatioii,  and  produce 
^sdfaod"   "-=*---  --  -'  "--^'    -T^e  tissues  irhidi  <&€}-  involve. 

Tims:  power  of  ..  .^--:.  -'--:  ^:--;-,^.  i.. .  -jnen  and  gelatine  may  be  rec- 
oganizerd  am  cnltnres  of  the  organism  grown  in  solid  gelatine  and 
soOadafied  Mood  isenmm,  tiiese  media  being  dissolved  by  peptonizing 
eaazyimes  prodimoed  by  Jlae  lacteria.  Leber  has  pointed  oat,  however, 
ttiaat  iagaaefoctiocEi  of  tiae  tissntes  is  to  some  degree  dae  to  the  influence 
©ff  tine  eanaigTated  leucocytes  or  a  jsrofceolytic  enzymt.  given  off  by 
ItJaese  cdDls;  for  example,  the  lifoefaction  attending  streptococcus  in- 
fedtaonas  aairaisit  of  aaecessit}-  he  caused  by  "fee  cells,  as  these  organisms 
do  aaot  llagsaefy  itSae  atoove  naentioned ' "  ~ '  ^ia. 

I^  appeare  as  a  'dul!  3-ellow,  ->.„,... r..-g: ten  or  graiiish- white 
ihmid,  opagaae  aaad  creaany,  thin  and  irmlky  or  more  thick  like  egg- 
aUBaaaanein,  aDOGfirdaaag  to  l3ae  amount  of  plasma  it  contains,  becoming 
!re«3dMiHginay  or  of  a  caie-S3i-1ait  color  in  case  of  greater  diapedesis 

V-  red  (Dorpmsdks.  It  is  often  mixed  with  fibrin  in  the  form  of 
^mmaRH  ^  -       -       .  wiuada  gives  the  pus   a   dough}-  consistence 

-' :  •  ..lemt  issrmdaie)  aaad  fills  the  tissues  with  a  fine  reticulated 

str.  ;:  -  - 

''-  :•  ■'•';  ."-fscope  pus  shows  great  numbers  of  leucoc}i:es, 
-•  ■  .1  p--j:  "  "  '  '!}-morf'-' ---'•" -ar  t\-pe.  showing  instead 
..:  -  -~'—j~  '..„_  :.  „  ...^5  a  r._j;.  .tr  of  nodular  Ctectiit  and 
die  t:-.:-L;  :.::'=^'  ^-nd  fragmented  portions  of  nucl^ir  substance. 
TBne  icomtiimal};^'  '  • ;  .  'ating  leiacoc}'tes,  among'  which  are  also  mono- 
aaaadlear  t;  l  -  :  fs.  ar^  sianilar  to  those  found  in  the  blood-  In  most 
off  jheptm^  aaad  C"  'I3-  im  alL  aaecinosis  is  recognizable  because  of 

TOirocfear  feagaaae'         '  and  naoire  certainly  hy  the  presence  of  fatt}- 


Pus. 


279 


degeneration.  The  colls  become  highly  granular,  the  protoplasm 
full  of  fat  vacuoles,  and  irregular,  and  finally  the  cells  become 
nothing  more  than  a  bunch  of  fat  globules  held  together  by 
the  protoplasmic  remains  (fatty  granular  cells)  or  falling 
apart  into  faffy  detritus.  The  leucocytes,  now  known  as  pits 
corpuscles,  and  incapable  of  further  motility,  are  suspended  in 
the    fluid    portion    of    the    exuded    plasma,    here    known    as    the 


Fig.    56. 

rus  from   cow;   unstained  microscopic  preparation  of   pus   cells    (highly   magnified). 

pus  scrum  {liquor  puris].  or  are  deposited  in  the  meshes  of  the 
tissue.  The  cells  of  the  tissue  in  which  the  suppuration  has  taken 
place  are  also  the  seat  of  marked  fatty  degeneration ;  the  connective 
tissue  corpuscles  and  cells  of  the  vessel  walls  often  exhibit  phagocytic 
appearances  and  are  found  with  leucocytes  englobed  within  their 
substance ;  and  in  chronic  inflammations  always  multiply,  thus  lead- 
ing to  restoration  of  the  lesion  or  its  encapsulation.     The  pyogenic 


28o 


Inflammation. 


bacteria  arc  usually  found  in  comparatively  large  numbers  in  the  pus 
serum  and  sometimes  the  leucocytes  are  loaded  with  them.  Accord- 
ing to  the  manner  of  commencement  of  the  process  a  single  variety 
may  be  found  present  as  a  perfectly  pure  culture,  or  there  may  be  a 
number  of  forms  associated  together.  As  occasionally  occurs  in 
chronic  cases,  if  no  microorganisms  can  be  discovered  it  may  be 
assumed  that  the  bacteria  have  gradually  died  in  the  pus  and  have 
undergone  disintegration.  If  the  suppuration  occurs  on  the  surface 
of  a  mucous  membrane  it  is  spoken    of    as    a    purulent  catarrh, 


^H 


^^ 


^i. 


ii;'t 


>' 


Fig.    57. 
I'ilni    preparation    of   pus    cells,    stained    with   fuclisin    (liighly    magnified). 

pyorrha-a,  or  blciiorrha'a  {^Xiuvn,  mucus;  pew,  to  flow).  In  such 
cases  the  blood  vessels  of  the  mucosa  and  submucosa  are  found 
dilated,  containing  large  numbers  of  leucocytes,  and  the  latter  cells 
profusely  accumulated  in  the  meshes  of  the  whole  mucous  mem- 
brane and  penetrating  between  the  epithelial  cells  of  the  surface. 
The  epithelium  is  loosened,  often  hanging  loosely  in  shreds.  In 
addition  the  formation  of  Jiiucus  is  increased,  and  many  epithelial 
cells  may  be  found  transformed  into  goblet  cells. 

This  viscid  secretion,  mixed  with  desquamated  epithelium  and 


Suppurative  Iiiflaiinnation. 


281 


emigrated  leucocytes,  constitutes  the  tluid  catarrhal  secretion.  On 
serous  surfaces  exudation  is  also  attended  with  desquamation  of 
the  endothelial  cells,  antl  the  exudate  accumulates  in  the  cavity 
lined -by  the  serous  membrane.  A  collection  of  pus  in  one  of  the 
larg-e  structural  cavities  of  the  body  (pleura,  joint,  antrum  of  High- 
more)  is  called  an  empyema  {^n-wveiv,  to  contain  pus).  When  pus 
is  distributed  all  through  the  spaces  and  meshes  of  tissue,  it  gives 
the  latter  a  dull  yellowish-white  or  gray  color  and  can  be  expressed 
irom  it  in   drops  by  squeezing  between  the  fingers   (purulent  infil- 


a  — 


Fig.   u8. 

riuulent  nephritis  of  mixed  type,  from  calf:  «.  microscopic  abscess:  h.  eml)oliis :  c. 
normal  urinary  tubules :  d.  urinary  tubules  devoid  of  their  epithelium,  con- 
taining  coagulated   material. 


tration).  Where  it  collects  in  larger  lymph  spaces  or  occurs  in  cav- 
ities formed  by  local  liquefaction  of  the  tissue,  it  constitutes  an 
abscess  (pus  sac),  that  is,  a  hollow  space  filled  with  pus;  from  pro- 
gressive tissue  destruction  and  continued  entrance  of  leucocytes 
such  an  abscess  may  attain  considerable  dimensions  (size  of  a  fist 
or  head).  A  circumscribed  collection  of  pus  in  the  stratum  Mal- 
pighii.  elevating  the  keratous  epiderm  over  it.  constitutes  a 
pustule  (pus  vesicle).  When  a  ])urulent  infiltration  extends  over  a 
large  area  of  subcutaneous,  subiiuicous  or  other  loose  cellular  tis- 


282 


IiiHanimation. 


sue,  with  production  of  spaces  filled  with  pus  and  confluence  of 
abscesses  the  condition  is  called  a  phlegmon.  Where  the  tissue  soft- 
ening or  the  gravitation  of  the  pus  into  dependent  positions  allows 
the  exudate  to  escape  the  abscess  is  said  to  break  or  perforate ;  and 
if  in  such  instances  there  are  formed  narrow  canals  lined  with  pus 
and  reaching  to  the  surface  these  are  called  fistnlcv.  A  loss  of  sub- 
stance upon  the  external  surface  or  in  mucous  membranes  caused 
by  suppurative  destruction  of  the  tissue  is  known  as  an  ulcere  the 
process  as  ulceration. 

In   chronic   suppurations  in  the   zone  between   the   dead  tissue 
breaking  down  into  pus  and  the  normal  tissues,  there  occurs  a  fibro- 


Fig.  59. 

Section   through  a  calf's   kidney   ricldlecl   witii  embolic  abscesses  ;   calyces  and   pelvis 

full   of   purulent   masses. 

angioplastic  proliferation,  as  a  bacony,  light  gray,  firm  tissue.  The 
suppurating  focus  is  encapsulated  by  this  demarcating  growtli,  that 
is,  it  is  enclosed  in  an  abscess  wall,  which  on  its  inner  surface 
usually  has  a  grimy,  grayish-yellow  or  slate-gray  color.  As  long  as 
virulent  pyogenic  bacteria  exist  in  the  cavity  this  abscess  membrane 
continues  to  give  rise  to  more  pus  [only  in  the  sense  that  the  exuda- 
tive processes  which  underlie  the  appearance  of  the  leucocytes  and 
fluid  are  largely  going  on  within  it,  and  not  in  the  sense  of  a  secre- 
tion as  formerly  believed]  in  the  focus,  for  which  reason  it 
is  sometimes  known  also  as  a  pyogenic  membrane.  The  involuntary 
muscle  and  elastic  tissue  of  arteries  exhibit  marked  resistance  to 
purulent  softening;  in  suppurative  cavities,  as  of  the  lungs  or  udder 
or  of  a  muscular  tissue,  vessels    are    often    found   as   bridge-like 


n(iViiorrliai:;ic,  CJangrenons  IiiHaimiutlioiis.  283 

bands  running  across  the  space,  perhaps  as  thick  as  a  lead  pencil, 
their  walls  not  destroyed  by  the  suppurative  process  but  hardened 
by  cicatricial  proliferation  and  resisting  destruction. 

The  vascular  connective  tissue  which  develops  upon  exposed 
suppurating  surfaces  (ulcers,  surfaces  of  wounds)  presents  a  red- 
dish-gray color  and  a  granular  or  finely  nodular,  uneven  appearance 
{gramilatioii  tissue)  ;  purulent  exudate  arises  from  this  also  so  long 
as  the  microorganismal  cause  of  inflammation  continues  active.  This 
tissue  serves  to  restore  the  tissue  loss,  filling  out  the  cavity  into  scar 
tissue  (cf.  Regeneration). 

With  multiplication  of  the  pyogenic  organisms  in  the  affected 
tissue  not  only  does  the  local  suppurative  inflammation  become  cor- 
respondingly prolonged,  but  there  arises  the  probability  of  its  exten- 
sion. The  bacteria  advancing  along  the  lymph  spaces  give  rise 
to  fresh  inflammatory  reaction  in  a  constantly  expanding  area.  The 
fact  that  the  leucocytes  have  wandered  into  the  suppurating  area, 
may  take  up  some  of  the  bacteria  and  carry  them  some  distance 
away,  until  stopped  by  the  occurrence  of  paralysis  and  death 
and  their  transporting  function  thus  ended,  gives  an  excellent 
opportunity  for  the  entrance  of  pus-producing  germs  into  the  lymph 
channels,  lymph  nodes  and  even  tlie  blood.  Malignant  and  activelv 
multiplying  organisms,  over  which  the  bactericidal  forces  of  the 
blood  have  no  influence  and  the  phagocytic  cells  no  power, 
are  thus  likely  to  set  up  new  foci  of  suppuration,  so-called  metas- 
tatic suppuration,  in  the  lymph  glands  and_  any  other  places  into 
which  they  have  been  carried  as  emboli. 

We  speak  of  iKTinorrhagie  iiiflammatioii,  where  the  exudate 
contains  a  notable  admixture  of  red  blood  cells,  and  is  consequently 
of  a  reddish,  grayish-red  to  dark  red,  chocolate  or  cafe-au-lait  ap- 
pearance. Serous  as  well  as  fibrinous  and  purulent  exudates  mav 
assume  this  character,  which  may  be  regarded  as  indicative  of 
some  especially  severe  disturbance  of  the  vessel  walls,  which  in 
turn  has  occasioned  marked  slowing  of  the  blood  current  in  the 
inflamed  part,  diapedesis  of  the  erytlirocytes  or  actual  rupture  of 
the  vessels,  and  is  therefore  accompanied  by  stasis  and  haemorrhage. 

Putrefaction  of  the  exudate  and  of  the  inflamed  tissue  {ichorous, 
gangrenous  or  putrid  inflammation)  is  necessarily  the  result  of  the 
invasion  of  putrefying  bacteria  into  the  necrotic  tissue  and  the 
masses  of  blood  and  exudate,  dead  material  like  the  tissue  itself.  This 
combination  of  inflammation  and  moist  gangrene,  or,  rather,  the 
secondary  changes  produced  by  gangrene,  breaks  down  the  tissue 
or  exudate  into  a  dirty,  grayish-green  or  dark  green,  malodorous 


284  Inflammation. 

material  and  indicates  an  unfavorable  prognosis  for  the  inflamma- 
tion because  of  tlie  almost  unavoidable  absorbtion  of  toxic  matter 
into  the  fluids  of  the  body. 

All  chronic  inflammations,  whatever  the  character  of  the  exu- 
date, result  in  the  production  of  vascular  connective  tissue ;  the 
existence  of  a  bacony,  indurated,  semitransparent  or  opaque  milky 
tissue  in  or  about  an  inflammatory  area  is  a  distinct  evidence  of 
its  chronicity.  This  is  said  to  be  a  productive  iniiammution.  What 
factors  are  responsible  for  this  tissue  formation  cannot  be  definitely 
determined.  It  may  be  assumed  that  the  same  chemotactic  in- 
fluences, which  are  at  the  bottom  of  the  escape  of  the  leucocytes 
from  the  vessels,  stimulate  the  physiological  formative  energy  of 
the  cells,  in  other  words  exert  a  demand  for  growth.  The  young 
cells  derived  from  these  fixed  cells  are  capable  of  some  degree  of 
motility  and  indeed  do  move ;  and  the  growing  connective  tissue  cells 
and  endothelial  cells  are  forced  to  take  the  direction  in  which 
chemotactic  and  nutritive  materials  are  located.  The  primary  exu-' 
date,  especially  fibrin,  possesses  this  power  of  attraction,  the  fibro- 
blasts beneath  a  fibrinous  covering  being  found  actively  proliferat- 
ing and  pushing  into  the  fibrin.  It  is  possible  that  the  infiltration 
of  a  tissue  with  exudate  directly  occasions  an  excessive  nutrition 
of  the  cells,  enabling  them  to  form  more  protoplasm  and  then  di- 
vide ;  and  again  the  formation  of  spaces  and  the  loss  of  substance 
of  the  tissues  should  be  considered,  these  factors  favoring  the  de- 
velopment of  inflammation,  and  having  a  tendency  to  increase  physi- 
ological regeneration  by  release  of  tissue  tension.  The  area  of  the 
proliferation  depends  upon  the  extent  and  duration  of  the  inflam- 
mation. As  already  stated,  the  embryonic  tissue  appears  in  the  form 
of  granulations  upon  free  surfaces  (wounds,  ulcers,  fistulous  pas- 
sages, serous  membranes).  With  a  reddish-gray  or  fleshy  red  color, 
it  presents  a  granular,  uneven,  undulating  surface,  from  which  in 
aseptic  inflammation  is  given  ofif  a  serous,  reddish,  viscid  exudate, 
or  when  bacteria  are  present  a  purulent  fluid.  The  granular  appear- 
ance which  gives  to  the  tissue  its  name  (grainihiiii,  a  small  grain) 
is  due  to  the  projection  of  the  outward  growing  capillaries  which 
extend  out  in  loops  and  intertwine  about  the  arteries  like  the  top 
branches  of  the  trees  in  a  leafy  wood.  The  precise  tint  of  the 
granulation  tissue,  at  times  more  deeply  red  or  again  more  grayish 
red,  depends  upon  the  relative  engorgement  of  the  capillaries  or 
the  predominance  of  the  gray  color  of  the  cells  lying  between  the 
vessels.  These  intercapillary  cells  are  leucocytes  and  fibroblasts, 
usually  spindle  shaped.    On  serous  surfaces  granulation  tissue  is  apt 


Chronic  Inflammation. 


285 


to  present  a  villous  appearance,  with  finger-like,  reddish  and  later 
whitish  processes  (filaments)  ;  growing  in  a  lluid  exudate  this  new 
tissue  is  found  floating  and  waving  back  and  forth  with  the  move- 
ments of  the  viscera.  When  there  is  motionless  contact  with  an 
opposed  and  similarly  inflamed  surface,  the  two  surfaces  become 
adherent,  at  first  by  the  embryonic  tissue,  but  later  by  capillary 
anastomoses  and  the  thorough  interlacing  of  the  developing  tissue. 
Thus  adiicsivc  inflammation,  the  formation  of  adhesive  bands,  often 
in    the    form    of    broad    connective    tissue    cords,    results.      When 


Fig.    60. 
Granulation    tissue    from    skin    of    horse. 

the  embryonic  tissue  develops  beneath  a  serous  surface  it  may  give 
rise  to  broad  flat  pale  areas  of  thickening,  the  so-called  milk  patches. 
About  abscesses  it  forms  abscess  walls;  along  fasciae  or  extending 
along  other  connective  tissue  structures  (submucous,  subcutaneous 
tissue  or  about  fistulous  passages)  it  forms  extensive  indurated 
layers.  When  the  process  involves  the  connective  tissue  structures 
of  an  organ  diffusely,  as  between  the  columns  of  liver  cells  or  in 
the  kidney,  this  interstitial  inflammation  occasions  a  widespread 
firm  induration  of  the  organ  {indurative  intlammation).  The  in- 
flammatory embryonic  tissue  gradually  becomes  pale  and  firm  and 


0--  THF 


'~^F 


286  Inflammation. 

tough,  the  young  fibroblastic  elements  like  the  cells  from  which 
they  were  derived  giving  rise  to  a  fibrillar  intercellular  substance 
(cf.  Regeneration).  The  bundles  of  fibrils  continually  growing 
thicker  add  firmness  to  the  tissue,  and  with  the  cessation  of  inflam- 
mation the  young  tissue  shrinks  gradually  to  smaller  bulk.  By 
such  changes  it  is  transformed  into  scar  tissue,  here  producing  the 
depressed  scars  of  surfaces,  there  constricting  the  lumen  of  tubes 
(stenosis,  atresia),  or  again  permanently  and  securely  enclosing 
necrotic  tissue  or  foreign  bodies  (encapsulation).  Productive  in- 
flammation usually  stops  when  the  lesion  which  caused  the  inflam- 
mation has  been  finally  dealt  with,  that  is  after  elimination  or  en- 
capsulation of  the  foreign  body,  necrotic  tissue  or  other  substance 
which  originated  the  inflammatory  process.  Where,  however,  the 
irritation  continues  and  final  cicatrization  is  delayed  tlie  prolifera- 
tive changes  sometimes  take  on  an  exuberant  character.  This  may 
be  particularly  well  seen  in  superficial  granulations,  which  may 
grow  up  out  of  the  lesion  as  projecting  tumor-like  masses  (zvild 
flesh,  caro  lu.vnrians,  granuloma)  [proud  flesh]  perhaps  as  large 
as  a  human  head.  Indeed,  interstitial  proliferation  of  fibroblasts 
proceeding  uninterruptedly  for  a  long  time  may  produce  a  mass  of 
young  inflammatory  tissue  far  in  excess  of  the  original  tissue  it 
replaced  and  producing  huge  connective  tissue  enlargements  {fihro- 
matous  inflammation,  fibrous  hypertrophy^).  On  mucous  membranes 
as  that  of  the  gall  bladder,  such  proliferations  meet  but  little  re- 
sistance from  the  fluid  in  the  cavity  and  often  give  rise  to  villous 
enlargements    (polyps). 

Specific  Inflammations. — There  are  a  number  of  parasitic  micro- 
organisms or  infections  which  induce  inflammatory  changes  but 
which  give  rise  to  tissue  reactions  of  such  special  peculiarity  that  it 
is  possible  to  conclude  the  agency  of  some  one  special  infection 
from  the  nature  of  the  inflammatory  proliferation  and  the  changes 
which  take  place  in  the  products  of  the  inflammation.  Although 
the  ordinary  inflammatory  irritants,  the  thermic,  toxic  and  mechani- 
cal causes,  act  according  to  the  intensity  of  their  influence  to  cause 
now  this  now  that  type  of  exudate,  there  are  some  causative  in- 
fluences which  give  rise  to  inflammatory  reactions  invariably  having 
the  same  appearance  and  constant  characteristics.  These  infectious 
agents  are  said  to  act  specifically  (that  is  peculiarly).  Usually  these 
types  of  disease  are  considered  under  special  names,  and  will  here 
be  treated  of  in  special  chapters  (v.  Tuberculosis,  Actinomycosis, 
Botryomycosis,  Glanders). 


Parciichyiiiafous  Iii/hunination.  287 

Parenchymatous,    Degenerative    Inflammation.—  The   inflammatory    pro- 
cesses   almost    exclusively    run    their    course    in    the    vascular    connective 
tissue  of  the  organ;   the  other   constituents,  gland  cells,   muscles  or  nerves, 
take   a   more  or  less  passive   part.     Inasmuch,   however,   as  there  may  often 
be    noted    in    the    tissue    elements    constituting    the     organic     parenchyma 
mitntivc    disturbances    and    regressive    metamorphoses,    either    as    primary 
changes    produced    by    the    cause    of    the    inflammation,    or    as    secondary 
alterations,  due  to  the  inflammatory  process  itself,  it  has  become  more  or 
less  customary  to  speak  of  such  instances  under  the  names  parenchymatous 
or     degenerative     inflammatiou.      Due     to     the     action     of     irritants     which 
primarily   cause   inflammatory   changes   in   the   interstitial   tissue,   there   often 
occur    such   changes   as   cloudy   swelling,    fatty    degeneration   or    necrosis    m 
parenchymatous    organs    like    the    liver,   kidneys    or   brain,    of    so   marked    a 
character  that  the  real  signs  of  inflammation  in  these  cases  almost  entirely 
disappear,  and  perhaps  can  only  be  demonstrated  by  means   of  the  micro- 
scope.     The    process    and    condition    might    well    be    summarily    relegated, 
because  of  its  principal  features,  to  the  degenerations.     As  the  type  of  the 
degeneration  is  sometimes  a  complex  one,  made  up  of  a  number  of  forms 
of    regressive   changes,   it   is    customary    when    some   of   the   other    features 
of    inflammation    coexist    (hypersemia,    swelling,    induration)    and    the    gross 
anatomical    picture    does    not    necessitate    their    separation,    to    employ    the 
term  "degenerative  inflammation"  for  the  combination  of  the  two  processes. 
[The   editor   feels   that  here   too  much   stress   is   laid  upon   the  passivity 
of   the  parenchymatous   tissues   in   inflammation.      They   are,   it   is   true,    not 
the    elements    which    strikingly    react    in    the    process,    and    their    regressive 
changes    are    usually    much    more    apparent    than    their    active    participation. 
Yet  they  do  react  and  in   practically  the   same  way,   as  by   proliferation,  to 
some    degree    in   this    or   that    inflammatory    process.      A    hepatitis    is    more 
apt,    it   is   true,   to   exhibit   the    liver   cells    swollen   and   granular,   yet   occa- 
sionally     there      are      found      cells      with     karyokinetic     figures      in      their 
nuclei ;    direct    nuclear    division    is    not    infrequently    seen    in    the    nuclei    of 
muscle    fibres    in    the    case    of    myositis ;    the    axis    cylinder    buds     in    the 
inflammation    caused   by   traumatic    injury   of   a    nerve,   or    the    new    growth 
of  muscle  spindles   in  the  inflammation  about  a   similar  lesion   of   muscular 
tissue,    argue    to    the    same    end.      Proliferation    commonly    takes    place    in 
the   epithelium  of  an   inflamed  mucous  membrane   or  in  a  gland,  and  while 
parenchymatous    cells   probably   take   no    part    in    ordinary   encapsulation    of 
foreign   bodies,    they   may   take    part    in    elimination.      They    probably    exert 
no    unimportant    part    in    the    destruction    or    dimunition    of    virulence    of 
many    toxic    chemicals,    as    is    a    generally    accepted    function    of    the    liver ; 
and    their    aid    in    excretory    elimination    from    the    body   of    the    same    type 
of   irritants,   and    in   a   minor   measure   of   particulate   elements,   as   unfit   and 
perhaps    harmful    albuminous    granules,    cannot    be    overlooked.      That    they 
are    in    a     way    phagocytic     is     evinced    by    their    assumption    of    pigment 
material,   changing   it,   i^  is  true,   in   many  cases  by  their   metabolic   activity. 
A   microorganism   may   lodge   upon    some   epithelial    cell   on   a   mucous    sur- 
face,  on  a   duct,  or  even   in   an   acinus   of   some   gland,   and    fail   to   be   dis- 
lodged.   The  cell  may  react  to  the  irritant  microbic  influences  by  pouring  out 
a    volume    of    secretion,    possibly    mucus,    in    which    the    microorganism    is 


288  Inflammation. 

caught  and  with  which  it  is  carried  away.  Or  the  microbe  may  destroy 
the  cell,  which  itself  then  becomes  a  further  source  of  irritation.  The 
cell  may,  it  is  true,  desquamate  from  mere  necrotic  loss  of  adhesion  to  its 
basement  membrane ;  but  at  times — and  too  soon  to  permit  of  classing 
the  phenomenon  as  anything  but  tlie  result  of  an  inflammatory  prolifera- 
tion— one  or  more  young  cells  grow  up  at  its  base  and  dislodge  the  cell 
with  its  bacterial  burden,  both  being  carried  off  by  the  fluid  on  the 
surface  (as  in  a  proliferative  catarrh).  As  far  as  the  proliferative  feature 
of  inflammation  is  concerned,  it  is  essentially  the  same  as  the  author  has 
detailed  in  the  chapter  on  Regeneration ;  regeneration  is  one  part  of 
inflammation.  Therefore  it  may  be  probably  claimed  that  in  some  meas- 
ure, often  insignificant,  it  is  true,  but  in  some  cases  clear  and  well  marked, 
all  the  capabilities  detailed  as  regenerative  for  parenchymatous  cells  are 
possible  for  inflammation.  One  should  therefore  be  willing  to  accept  a 
proliferative  parenchymatous  inHammatioii  as  well  as  the  more  striking 
degenerative  inflannnation,  which  alone  may  be  inferred  from  the  author's 
paragraph  as  characterizing  parenchymatous  structures  in  the  inflammatory 
process.  Moreover,  from  a  theoretical  standpoint,  what  has  just  been 
said  may  be  understood  as  indicating  that  parenchymatous  cells  are 
capable  of  participating  in  all  the  ways  ascribed  to  other  fixed  cells ; 
practically  they  do  not  manifest  such  ability  in  a  degree  comparable  to 
that  exhibited  by  the  connective  tissues.  These  features  are  considered 
further  on  by  the  author,  who  would  exclude  as  normal  some  of  these 
minor  reactions.] 

The  nomenclature  and  classification  of  inflammatory  processes 
include  consideration^  of  the  retiology  {traumatic,  toxic,  thermic, 
infections  inflammations) ,  the  duration  of  the  process  {acute,  sub- 
acute, chronic)  and  the  form  of  exudate  and  other  anatomical  fea- 
tures {fibrinous,  serous,  purulent,  etc.). 

The  scientific  name  {terminus  technicus)  used  to  express  an  in- 
flammation of  an  organ  is  constructed  by  adding  to  the  root  of  the 
Latin  or  Greek  word  for  the  organ  tlie  termination  itis  (really  from 
the  feminine  form  of  the  major  name  ending  in  ,js)  ;  for  example, 
wXevpa.,  lining  of  chest' cavity,  irXevptT-ns ,  one  suffering  in  the  pleura, 
irXevpiTLs  1  supply  vosds ) ,  inflammation  of  the  pleura.  In  this  way  for 
example  are  built  up  such  words  as :  gastritis,  inflammation  of  the 
stomach;  arthritis,  inflammation  of  a  joint;  peritonitis,  inflamma- 
tion of  the  peritoneum ;  osteitis,  inflammation  of  bone,  etc.  In 
case  of  inflammation  of  the  serous  covering  of  an  organ  the  prefix 
"peri"  is  added  to  flie  name  (irepl,  about,  around)  ;  in  inflammation 
of  the  connective  tissue  alongside  of  rn  organ,  the  prefix  "para" 
(Trapa,  alongside)  ;  for  example  metritis,  perimetritis,  parametritis. 
Special  names  are  applied  to  some  inflanimations :  pneumonia  (not 
pulmonitis)   for  pulmonary  inflamniattqn,;  angina  for  infl.amrnation 


Termination  of  Inflammation.  289 

of  the  soft  palate  and  neighboring  structures ;  coryca,  for  nasal  ca- 
tarrh; erysipelas  for  a  special  inflammation  of  the  skin. 

As  above  stated  inflammation  is  a  local  reactive  process  in  which 
the  mechanisms  of  tlie  body  underlying  its  protection  from  harmful 
influences  and  its  compensation  for  disturbances  are  aroused  to  an 
especially  intense  activity.     This  defensive  and  compensatory  func- 
tion exists  even  in  normal  conditions,  as  a  vital  cellular  phenomenon 
of  the  animal  body.     Reactions  of  the  same  kind  are  almost  all  the 
time  going  on  in  the  system ;  here  and  there  cells  are  dying  and  are 
being  made  away  with  by  phagocytosis,  and  are  being  replaced  by 
regenerative  proliferation.     ^Microorganisms  are  deposited  at  many 
points  on  a  mucous  membrane  in  communicating  relation  with  the 
outside  world  and  are  rendered  harmless  by  phagocytosis ;  in  the 
stomach   and   intestinal   canal   there   often   accumulate   toxic    sub- 
stances,   formed    from   the    food,    which    cause    a    hyperaemia    and 
are    swept    away    by    the    increased    secretion,    or    are    taken    up 
by    the    emigrated    leucoc}i;es     (being    quickly    rendered    inert    in 
the    liver)    and    only    transiently    excite    some    of    the    individual 
inflammatory    phenomena.      Insignificant    and    minor    grades    of 
inflammation    are    thus    not    infrequently    induced,    but   these    are 
not  classed  as  inflammations.     They  are  regarded  as  physiological 
phagocytosis,  functional  hyperaemia,  physiological  regeneration,  each 
running  its  individual  course;  they  are  not  considered  as  disturb- 
ances.    We  only  speak  of  inflammation  when  these  reactive  phe- 
nomena occur  together  and  in  unusually  marked  degree  and  when 
the  causative  injury  or  the  reactive  process  itself  is  productive  of 
functional  faults  in  the  affected  part. 

Termination  of  Inflammations. — Since  inflammation  in  many  in- 
stances serves  successfully  to  do  away  with  useless  and  injurious 
materials  and  to  restore  the  injured  tissue  or  at  least  to  replace 
faults  with  cicatricial  tissue,  it  may  be  looked  upon  as  a  regulative 
and  defensive  effort  of  important  use  to  the  economy.  In  this  adap- 
tive eft'ort.  with  much  propriety  of  comparison,  the  advancing  leu- 
cocvtes  mav  be  likened  to  mobilized  troops  or  to  a  body  of  street 
cleaners ;  but  it  cannot  be  said  that  the  cells  of  the  body  pursue  any 
fixed  plan  of  procedure  always  under  nervous  control,  but  rather  that 
the  whole  process  is  in  reality  the  occurrence,  it  may  be  said  the 
accidental  occurrence,  of  phenomena  of  physiological  motility  and 
secretion  of  living  protoplasm  excited  by  external  stimuli.  The 
physiological  component  processes  of  inflammation  are  the  same  as 
the  cellular  functions  of  phagocytosis  and  secretion  which  take 
place  in  digestion,  the  result  of  mechanical  and  chemical  excitation, 


290  Inflamination. 

peculiar,  however^  in  that  these  cellular  activities  are  not  confined  to 
any  single  organ  but  extend  to  all  the  organs,  to  the  vascular  con- 
nective tissue  framework  of  all  parts  of  the  body. 

The  favorable  or  unfavorable  outcome  of  inflammation  depends 
upon  accidental  factors,  upon  the  nature  and  mode  of  action  of  the 
causative  agents,  upon  the  location  of  tlie  part  injured  and  the  de- 
gree of  functional  disturbance  which  the  inflamed  organ  experiences. 
Of  the  individual  reactions  which  in  combination  constitute  inflam- 
mation, it  can  be  accepted  that  phagocytosis  removes  structures 
killed  by  harmful  foreign  bodies,  that  the  exudation  exerts  a  di- 
gestive action  upon  and  washes  away  injurious  substances,  that  the 
blood  plasma  (and  possibly  too  a  secretion  given  off  from  the  leuco- 
cytes) supplies  antitoxic  substances,  and  that  the  tissues  are  brought 
into  a  state  of  regenerative  ability  by  the  increased  nutritive  supply. 
AH  of  these  factors  combine  to  bring  about  compensation  for  the 
influences  of  a  variety  of  harmful  agencies.  When  the  irritant  is 
removed  or  encapsulated  the  condition  of  special  stimulation  ceases 
and  the  inflammation  ends  m  resolution,  because  no  more  fresh  cells 
advance  into  the  area  and  those  which  have  previously  escaped  from 
the  vessels  either  break  down  and  are  reabsorbed  as  detritus  with  the 
other  i)arts  of  the  exudate  by  the  veins  and  lymphatics,  or,  in  case 
they  retain  their  power  of  movement,  pass  off  to  other  places  toward 
which  they  are  attracted  by  nutrient  matter. 

The  inflammatory  process  cannot  invariably  bring  about  com- 
plete regeneration  of  destroyed  tissue ;  as  a  rule  onlv  the  connective 
tissue  is  fully  replaced,  the  specific  elements  which  are  lost,  as 
glandular  or  ganglionic  cells,  not  being  reformed.  It  is  in  this  way, 
by  the  formation  of  connective  tissue  to  occupy  the  space  of  a  lesion, 
that  inflammation  brings  about  healing  of  the  lesion.  The  inflamma- 
tory connective  tissue  growth  which  paves  the  way  for  encapsula- 
tion of  foreign  bodies  and  demarcation  of  dead  tissue  is  in  the  same 
way  to  be  regarded  as  an  attempt  at  healing. 

However,  there  are  also  disadvantageous  features  connected  with 
inflammation.  Adhesions  between  organs,  the  occupation  of  cavities 
by  masses  of  exudate,  as  in  the  lung  or  pleura,  exudative  effusions 
in  the  brain  or  in  the  kidneys,  occasion  functional  disturbances, 
which,  depending  on  the  importance  of  the  affected  organ,  may 
threaten  tlie  life  of  the  subject ;  and  inflammation  may  terminate  in 
death.  This  does  not,  however,  essentially  alter  the  conception  of 
inflammation  as  a  defensive  effort.  Ribbert  compares  it  to  an 
army,  which,  it  is  true,  is  in  the  main  a  valuable  organization,  but 
which  ma\'  fail  at  times  to  overpower  a  stronger  enemy  or  which 


Tiibcrcitlosis.  291 

may  from  the  cost  of  organization  and  armament,  financially  ruin 
a  land.  The  fatal  termination  and  the  local  disadvantages  of  the 
disease  are,  strictly  speaking,  not  attributable  to  the  inflammation 
but  to  the  causes  of  the  inflammation. 

Tuberculosis. 

Tuberculosis  is  a  contagious  infectious  disease  having  a  very 
wide  distribution  among  man  and  the  domestic  animals,  caused  by 
the  tubercle  bacillus  discovered  by  Robert  Koch  in  1882,  and  char- 
acterized anatomically  by  the  formation  of  minute  nodular  inflam- 
matory foci  (tiibcrculuiu,  a  small  node)  which  uniformly  undergo 
necrotic  disintegration  and  by  their  progressive  increase  destroy  the 
tissue  involved  by  them. 

This  malady,  the  most  common  of  all  diseases,  manifests  itself 
in  man  generally  as  a  pulmonary  affection  of  years'  duration,  causing 
pulmonarv  zvasting  and  consumption  (phthisis,  iromcpdlu,  to  waste, 
consume) ,  but  also  producing  painful  destruction  of  bones  and  joints, 
ulceration  of  the  intestines,  and  tuberculous  disease  of  the  lymph 
nodes,  brain  and  other  structures.  Year  after  year  tuberculosis  car- 
ries ofif  over  a  million  people  in  Europe,  or  nearly  three  thousand 
every  day,  and  must  therefore  be  regarded  as  the  most  deadly  of  all 
plagues,  decimating  the  populace,  and  hurrying  to  death  the  effi- 
cient youth  and  destroying  the  earning  capacity  of 'families  by  the 
tedious  course  of  the  afifection  and  death  of  their  members. 

The  disease  is  no  less  a  calamity  to  the  cattle  industry.  Among 
domestic  animals  cattle  and  swine  are  most  frequently  affected; 
ten,  twenty,  yes  eighty  per  cent,  of  the  cattle  brought  to  the  larger 
stock  yards  in  some  districts  are  diseased.  The  financial  losses  oc- 
casioned by  the  affection  of  so  many  animals  may  be  estimated  by 
hundreds  of  thousands  of  dollars  annually,  for  these  include 
such  varied  elements  as  loss  of  weight  and  forced  slaughter,  impair- 
ment of  milk  production  and  of  edibility  of  the  meat,  and  sterility  or 
transmission  of  the  disease  to  offspring.  Tuberculosis  in  cattle  be- 
comes doubly  important  when  the  danger  to  human  health  is  con- 
templated, because  the  milk  of  animals  with  tuberculosis  of  the  udder 
can  transmit  the  disease  to  children  and  adults. 

The  effort  to  overcome  this  infectious  disease,  which  has  been 
continuallv  on  the  increase  during  recent  decades  in  man  and  in 
animals,  has  therefore  come  to  be  one  of  the  most  important  aims  of 
medicine,  an  object  of  municipal  and  national  thoug-ht,  and  a  matter 
of  interest  both  to  the  community  and  to  the  individual. 


292  specific  Inflammations. 

The  communicability  of  pulmonary  consumption  was  suspected 
even  by  the  physicians  of  antiquity  (Hippocrates,  Isocrates)  and 
had  obtained  some  credence  among  the  laity.  ]\Iore  or  less  energetic 
measures  (burning  of  beds  and  linen  used  by  consumptives,  disinfec- 
tion of  furniture  and  dwellings  by  means  of  smoke,  etc.)  were 
practiced  as  early  as  1750  at  Nancy,  1782  at  Naples  and  about 
the  beginning  of  the  nineteenth  century  were  ordered  and  carried 
out  by  authority  of  court,  but  were  without  result  because  of 
their  insufificiency  to  remove  all  the  factors  of  infection. 

According  to  Nocard*  phthisis  is  said  to  have  been  declared  a 
contagious  disease  in  one  of  the  Gothic  laws. 

Under  the  influence  of  the  erroneous  teaching  of  Broussais  that 
phthisis  arose  spontaneously  as  a  result  of  meteorological  conditions, 
social  misery,  etc.,  and  the  widely  spread  mistaken  conception  which 
prevailed  after  the  discovery  of  the  tubercle  bacillus  to  the  effect 
that  this  disease  germ  is  omnipresent  (ubiquitous),  efforts  toward 
prophylaxis  remained  restricted.    With  the  idea  that  predisposition 
was  the  most  important  fault  it  w'as  considered  impossible  to  root  out 
the  evil ;  or  it  was  held  that  the  difficulties  involved  in  the  campaign 
were  insurmountable  because  of  the   impracticability  of  enforcing 
the  necessary  rules  of  procedure.     The  old  suspicion  of  the  conta- 
gious character  of  the  disease  received  the  first  important  confirma- 
tion in  the  studies  of  Klencke   (1843)   ^"*^^  \'illemin   (1865-1868), 
the  latter  proving  by  a  series  of  positive  experiments  the  inocula- 
bility  of  human  tuberculosis  and  pearl  disease  of  cattle  into  rabbits, 
etc.,  and  establishing  the  identity  of  animal  and  human  tuberculosis. 
Thereafter  numerous   investigators   interested  themselves   in   Ville- 
min's  teaching  and  repeatedly  carried  out  similar  experiments,  some- 
times confirming,  sometimes  opposing  his  results.     (For  details  cf. 
writings  of  Johne  and  Nocard.)     With  the  discovery  of  the  tubercule 
bacillus  by  Robert  Koch  and  the  ingenious  labors  of  this  German 
investigator,  which  have  completely  unraveled  the  aetiology  of  tuber- 
culosis- of  man  and  animals,  all  doubts  as  to  the  nature  of  the  af- 
fection disappeared.     Koch  succeeded   in   discovering  and   demon- 
strating the  tubercle  bacillus  by  a  special  method  of  staining  devised 
by  him ;  and  it  is  always  possible  by  means  of  this  method  in  case  of 
tuberculosis  to  recognize  the  tubercle  bacillus  in  diseased  parts  and 
material  discharged  from  them  both  in  man  and  in  animals.     This 
microorganism  presents  itself  as  a  rod-shaped  microphvte,  from  two 
to   four  micromillimeters  in   length   and   from   three   to  five-tenths 

*  E.    Nocard,   Lea   Tuberculoses   Animales;   Encyclop^die    Scientlflque    des    Aide 
^rt'moire.     Paris :    Masson. 


Tuberculosis.  293 

micromillimeters  in  width  (about  one-fourth  to  three-fourths  the 
diameter  of  a  red  blood  corpuscle).  Koch  also  pointed  out  the  possi- 
bility and  methods  of  growing  the  tubercle  bacillus  in  artificial  nutri- 
tive media  outside  the  animal  body ;  and  thousands  of  experiments 
have  contributed  to  the  proof  that  by  inoculation  of  artificially  culti- 
vated germs  tuberculosis  may  be  reproduced  in  all  its  forms  in  any 
of  the  warm-blooded  animals. 

The    tubercle    bacillus     does    not 
grow  free  in  nature ;  occurring  only  v^    \ 

where  it  is  deposited  with  tuberculous         *"*"  V 

discharges.     It  multiplies  in  this  cli- 
mate but  not  outside  the  animal  body  ^        — 
and    only   within    the    organs    of   the       "Ny       "  ^ 
animal   or   human   economy.      In   the                     '/        v,         ^ 
free    state    the    germ    of   tuberculosis                                      — --x^ 
may   retain  its  vitality  and   virulence 
when    dried    and    in   the    dark    for   a 
long  time   (more  than  a  vear)  ;  but  a 

*  ^  -  Fig.    61. 

variety   of   conditions   may    serve    to      tubercle     bacilli     ia     bronchial 
render  the  infectious  material  harm-  ^ucus    of    cow;     x    about 

less  or  destroy  it.  Sunlight,  for  ex- 
ample, will  kill  the  organism  in  as  short  a  time  as  two  to  four 
hours  and  even  dififuse  daylight  will  destfoy  it.  Rain  has  a  favor- 
able influence  in  washing  away  the  vehicle  of  the  contagion  and 
thus  exposing  it  to  light;  a  temperature  of  50° -70°  C.  developing 
in  manure  wall  also  kill  it. 

For  such  reasons  tuberculosis  must  be  regarded  as  a  true  con- 
tagious affection.  Its  transmission  from  one  human  being  to  another 
occurs  chiefly  from  the  expectorated  sputum,  which,  dried  and  blown 
about  as  dust,  gains  access  to  the  pharynx  and  air  passages  by  in- 
halation, sometimes  a  portion  being  swallowed  and  finding  its  way 
from  the  intestines  into  the .  tissues  or  sometimes  infecting  the 
pharyngeal  tissues  and  air  passages.  Tiny  drops  of  saliva  or 
mucus  containing  the  organism  may  sometimes  be  discharged  in 
talking  or  sneezing  and  in  case  these  are  directly  inhaled  by  a 
second  individual,  or  if  they  fall  upon  the  food  and  are  ingested 
with  it,  they  may  give  occasion  for  development  of  tuberculosis. 
The  number  of  tubercle  bacilli  in  such  expectorated  matter  may  be 
enormous ;  in  a  single  drop  of  microscopic  size  there  may  be  hun- 
dreds and  it  has  been  estimated  that  one  consumptive  human  being 
may  give  off  seventy-two  hundred  millions  of  tubercle  bacilli  in  the 
course  of  a  single  day  (Heller). 


294  Specific  IiiHaDniiatioiis. 

The  contagion  is  carried  from  animal  to  animal  in  the  same  way. 
Cattle  and  hogs  affected  with  pulmonary  tuberculosis  discharge 
bronchial  mucus  loaded  with  tubercle  bacilli  by  their  coughing ;  and 
this  is  inhaled  as  fine  spray-like  droplets  by  other  animals  standing 
near  h\,  or  falls  upon  the  fodder  or  into  the  water  and  with  these 
substances  may  gain  entrance  to  a  new  animal  body.  One  of  the 
most  important  sources  of  tuberculous  infection  both  for  man  and  an- 
imals is  the  milk  of  cattle  affected  by  tuberculosis  of  the  udder  ; 
milk  from  such  a  source  may,  as  shown  by  Bangs,  remain  apparently 
normal  even  for  weeks  though  it  contain  millions  of  tubercle  bacilli. 
If  swallowed  in  raw  state,  as  used  in  the  feeding  of  calves  and  pigs, 
such  milk  gives  rise  to  infection  of  tlie  body  by  way  of  the  alimen- 
tary canal  and  chyle  vessels,  as  proved  by  experimental  feeding. 
The  general  milk  from  a  dairy  may  become  infected  if  there  be 
but  one  cow^  in  the  stalls  with  tuberculosis  of  the  udder,  provided 
that  cow  be  milked  with  the  rest  and  her  milk  mixed  with  that 
from  the  other  cows. 

Again  the  intestinal  discharges  of  consumptive  animals  contain 
the  infection,  either  because  these  animals,  as  is  often  the  case, 
have  tuberculous  ulcers  of  the  intestine,  the  bacilli  from  which  be- 
come mixed  with  the  excrement,  or  because  the  animals  swallow 
their  pulmonary  expectorate  and  the  bacilli  pass  through  the  bowel 
without  being  all  destroyed.  The  vaginal  discharge  from  cows  with 
uterine  tuberculosis  furnishes  another  source  of  infection.  Th'2 
straw  saturated  with  these  infectious  discharges,  should  it  happen 
to  be  eaten  by  other  cattle  with  their  fodder,  may  serve  as  a  means 
of  transmission  of  the  disease.  Occasionally  infection  occurs  in 
coition,  as  the  vaginal  secretion  may  be  carried  from  one  animal  to 
another  by  the  male,  or  the  latter,  when  tuberculous,  may  transmit 
his  own  bacilli  in  the  spermatic  fluid.  Tuberculous  infection  of 
cutaneous  wounds  is  rare  among  animals,  although  occasionally  in 
man  post  mortem  section  of  tuberculous  organs  gives  opportunity 
for  this  mode  of  infection. 

The  horse  is  usually  infected  with  tuberculosis  by  eating  straw 
(soiled  with  the  tuberculous  discharges  of  cattle)  ;  the  dog  often 
by  licking  up  human  tuberculous  sputum ;  the  cat  by  drinking  tuber- 
culous milk.  The  disease  develops  in  fowls  where  the  latter  have 
opportunities  to  pick  up  human  sputum  or  tuberculous  discharges 
from  horses,  cattle  or  hogs ;  the  excrement  of  chickens  already 
affected  with  intestinal  tuberculosis,  however,  affords  the  greatest 
chance  for  the  infection  of  the  other  feathered  inhabitants  of  the 
premises   (soiling  of  food,  ground,  etc.). 


Tuberculosis.  '  295 

Tuberculous  human  beings  and  animals  are  sources  of  further 
infection  only  as  they  throw  off  materials  containing  tubercle  bacilli. 
The  foci  of  the  disease  which  exist  within  the  animal,* shut  off  from 
the  exterior,  as  tuberculous  lymph  glands,  do  not  give  off  bacilli 
in  such  a  way  that  they  may  be  transmitted  to  another  animal. 
For  example,  the  milk  of  cows  which  do  not  have  tuberculosis  of 
the  udder  is  harmless  even  though  there  are  tuberculous  lymph 
glands  and  serous  membranes  in  the  animals ;  the  meat  of  a  tuber- 
culous animal  is  free  from  danger  as  long  as  it  does  not  contain 
actual  tubercles  or  as  long  as  the  lymph  nodes  situated  in  the  flesh 
remain  free  from  tubercle  bacilli.  (For  further  details  consult 
Ostertag:    Zeitsclir.  fiir  Flcisch-  unci  Milchhygiene,  1890-1903.) 

Concerning  the  question  of  inheritance  of  tuberculosis,  observa- 
tions running  over  a  number  of  years  upon  the  condition  of  calves 
born   of   tuberculous   cows,'  with   control   by   tuberculin   injections 
and  slaughtering  (Bang),  as  well  as  a  series  of  experiments  upon 
pregnant  tuberculous  guinea  pigs  (Gartner),  give  positive  informa- 
tion.    Tuberculosis  may  be  acquired  through  the  placenta.     Alany 
examples  of  this  have  been  found  in  newly  born  calves  and  children, 
and  occasionally  too  in  the  miscarried  foetus.     In  such  cases  the 
liver  and  periportal   lymph  nodes  are  invariably  involved  and  the 
disease  is  apt  to  be  more  or  less  distributed  to  other  lymph  glands 
and  organs.     When  it  has  been  possible  to  investigate  the  mother 
of  the  tuberculous  offspring,  invariably  a  tuberculous  affection  of 
the  uterus  and  sometimes  of  the  chorion  were  found.     The  tubercle 
bacillus   is   scarcely   likely  to  pass   directly   from  the  blood  of  the 
mother  to  the  foetus  (the  blood  is  separate  in  the  two  parts  of  the 
placenta)  ;  but  if  during  pregnancy  the  uterus  should  become  in- 
volved by  tuberculosis   (focal,  as  in  one  cornu)  the  tubercle  bacilli 
find  their  way   into  the  placental  milky  humor  and  penetrate  the 
fcEtal  placenta,  and  then  pass  with  the  blood  of  the  umbilical  vein 
to  the  liver  of  the  foetus.     In  this  way  the  latter  is  born  into  the 
world  a  subject  of  tuberculosis;  but  it  is  possible  that  after  birth 
the  disease  may  progress  very  slowly  and  remain  latent  for  months. 
A  conceptional  or  germinal  infection,  that  is  through  the  ovum  or 
spermatozoon,  is  so  improbable  that  it  may  be  said  to  be  entirely  iin- 
possible.     Supposing  the  possibility  that  a  fertilized  ovum  could  be 
infected  by  tubercle  bacilli,  it  would  die  from  the  caseating  influence 
of  these  germs  long  before  it  could  develop  into  an  embryo,  or  else 
the   embryo   in    its   earliest  stages  of  germ   vesicle  and   formation 
of  the  blastodermic  layers  would  already  be  but  a  degenerating  mal- 
formation.    When  it  is  remembered  that  of  the  millions  of  sperma- 


296  specific  Inflammations. 

tozoa  which  enter  the  female  genital  canal  in  coition  only  a  single 
one  passes  through  the  micropyle  of  tlie  ovum,  it  cannot  but  be  a 
strange  coincidence  that  just  this  very  one  should  carry  with  it  a 
tubercle  bacillus.  ("Tubercle  bacilli  in  the  sperm  are  scarcely  likely 
to  adhere  to  the  spermatozoa  but  are  more  likely  to  remain  in  the 
fluid.)  And,  too,  if  the  fertilizing  spermatozoon  accompanied  by 
a  bacillus  should  penetrate  into  an  ovum  the  bacillus  as  it  multiplied 
would  at  once  seriously  interfere  with  the  process  of  multiplication 
of  the  copulated  cells  and  quickly  put  an  end  to  the  embryonic 
germ  by  coagulation  necrosis.  The  assumption  tliat  tubercle  bacilli 
may  somehow  lie  dormant  in  an  ovum  in  course  of  embryonic  de- 
velopment, and  later  when  the  fcetus  has  been  formed  start  to  mul- 
tiply, is  without  foundation  and  is  in  contradiction  to  all  our  knowl- 
edge of  the  growth  of  vegetable  microorganisms  in  the  animal  body. 
[Mafucci's  experiments  in  chicken  eggs  (Centralbl.  f.  Bakt.  u. 
Parasitcnk.,  1889,  p.  237.)  are  usually  offered  as  contradicting  this 
contention.  He  inoculated  eggs  with  tubercle  bacilli  and  then  in- 
cubated them.  Out  of  eighteen  eggs  he  obtained  one  dead  and 
eight  living  chicks.  He  was  unable  to  find  tubercle  bacilli  in  the 
dead  chick,  and  examining  the  unfertile  and  rotten  eggs  which 
failed  to  hatch  he  was  unable  to  be  satisfied  of  any  growth  of  the 
tubercle  bacilli  in  them.  His  chicks  were  at  first  apparently  healthy, 
but  later  died  with  well  defined  tuberculous  lesions.  That  latency 
of  infections  is  possible  in  relation  with  embryonic  development  is 
also  indicated  by  the  transmission  of  the  psorosperms  of  pchrine, 
pointed  out  by  Pasteur,  through  the  ova  of  silk  worm  moths  to  the 
silk  worms,  which  at  first  seem  healthy  but  soon  die  from  the  dis- 
ease.] 

Attempts  to  prove  from  genealogical  tables  and  statistics  that 
there  is  a  true  hereditary  transmission  of  tuberculosis  from  parents 
to  offspring  must  always  meet  with  the  objection  that  children  or 
calves  may  be  born  free  from  the  disease  and  may  acquire  the  tuber- 
culosis in  the  first  years  of  tlieir  lives  from  living  in  the  presence  of 
their  tuberculous  parents.  The  above  principal  modes  of  trans- 
mission of  the  tuberculous  virus  have  been  proved  by  great  num- 
bers of  experiments.  With  human  tuberculous  sputum  as  well  as 
material  obtained  from  tuberculous  foci  of  the  lungs,  liver,  lymph 
nodes,  intestine,  etc.,  human  or  animal,  and,  too,  with  pure  cultures 
of  tubercle  bacilli,  typical  tuberculous  disease  can  be  caused  either 
by  feeding,  inhalation,  or  by  subcutaneous,  intraperitoneal  or  intra- 
venous injection  in  all  susceptible  species  of  animals.  There  are, 
however,  certain  differences,  or  rather  dissimilarities,  in  pathogenic 


Tuberculosis.  297 

ability  in  tubercle  bacilli  derived  from  human  beings  and  from 
various  types  of  animals,  referable  to  the  source  of  the  virus.  For 
example,  as  shown  by  R.  Koch  and  Schiitz  in  a  long  series  of  experi- 
ments, and  even  earlier  by  Putz  (1882)  and  Smith  (1896),  it  is  not 
as  a  rule  easy  to  render  cattle,  sheep  and  swine  tuberculous  by 
using  tubercle  bacilli  from  a  human  source  (even  in  case  of  inoc- 
ulation of  large  quantities)  ;  and  it  is  also  difficult  to  infect  birds 
with  tuberculous  material  derived  from  man  or  mammals.  These 
negative  results  at  first  caused  doubt  as  to  the  identity  of  the  tuber- 
culosis of  all  individuals.  However,  it  was  recognized  that  no  dis- 
tinct line  of  difference  could  be  drawn  between  the  organisms,  for 
even  a  few  positive  results  were  sufficient  to  show  the  identity  of 
the  affection  in  man  and  in  animals.  Positive  cases  of  the  kind  re- 
quired have  been  obtained  in  such  abundant  number  and  from  ex- 
periments of  indisputable  accuracy  that  the  possibility  of  infecting 
man  with  bovine  tuberculosis  and  of  the  transmission  of  human 
tuberculosis  to  the  domestic  animals  cannot  be  denied.  Besides  the 
older  experiments  of  Bollinger,  Klebs,  Chauveau  and  the  later  ones 
of  Sidney  Martin,  Frothingham.  Arloing.  de  Jong,  Stuurmann, 
Thomassen,  Prettner,  Klebs  and  Rievel  who  were  successful  in 
inoculating  cattle  with  tuberculous  virus  from  man,  tlie  examples 
collected  by  Johne.  Ostertag  and  Xocard  and  Leclainche  of  wound 
inoculation  in  man,  occasionally  actually  occurring  in  the 
course  of  slaughtering  operations  and  meat  inspection,  speak 
strongly  for  the  idea  that  bovine  tuberculosis  is  an  infection  of  no  lit- 
tle importance  to  man.  Important  contributions  have  also  been  made 
in  this  connection  by  Johannes  Fibiger  and  C.  O.  Jensen,  goihg  to 
show  that  tubercle  bacilli  virulent  to  man  may  also  be  highly  viru- 
lent to  cattle,  and  confirming  the  belief  that  many  cases  of  intestinal 
tuberculosis  in  children  are  properly  attributed  to  the  ingestion  of 
cow's  milk  containing  tubercle  bacilli,  von  Behring  arrives  at  the 
same  conclusion,  finding  that  some  strains  of  tubercle  bacilli  obtained 
by  culture  from  human  source  possess  high  grade  of  virulence  for 
cattle  while  other  strains  have  no  pathogenic  influence  for  cattle 
at  all.  Further  the  observations  made  by  Eberlein  and  Cadiot,  in- 
dicating the  acquirement  by  man  of  the  infection  from  tuberculous 
parrots  and  the  rather  common  transmission  of  the  disease  to  parrots 
from  consumptive  human  beings,  as  well  as  the  transmissibility  by 
inoculation  of  bovine  tuberculosis  to  apes,  proved  by  Nocard,  force 
the  assumption  of  an  ^etiological  relationship  of  the  disease  or  of  a 
family  identity  of  the  tubercle  bacilli  of  heterogeneous  derivation. 
[Recently  Koch  has  brought  forward  anew  the  idea  of  specific  dif- 


298  specific  Iiiflaiiu)iatio)is. 

ference  between  the  bacilli  of  human  and  bovine  tuberculosis,  but 
has  met  strong  opposition  at  the  hands  of  a  large  number  of  stu- 
dents. In  this  country  Ravenel  and  Pearson  have  shown  distinctly 
the  identity  of  the  microorganisms;  and  the  work  of  these  investi- 
gators in  inducing  immunity  in  cattle  against  bovine  tuberculosis 
by  vaccination  with  cultures  of  human  tubercle  bacilli  of  low  viru- 
lence is  of  extreme  significance.] 

The  variations  in  pathogenic  power  exhibited  by  the  bacilli  ob- 
tained from  different  sources  find  their  explanation  in  the  adaptation 
of  the  organisms  to  the  different  animal  bodies.  It  is  obvious  and 
reasonable  that,  in  case  of  transmission  of  consumption  which  has 
been  going  on  for  centuries  from  one  human  being  to  another,  in 
which  the  tubercle  bacilli  of  every  generation  always  grow  ex- 
clusively  in  the  human  body,  the  organisms  may  come  to  adapt 
themselves  to  the  conditions  of  nutrition  which  the  human  system 
supplies  to  them,  and  that  they  attain  their  greatest  infectious  power 
for  it  and  find  more  difficulty  of  growth  in  another  type  of  animal 
body.  In  the  same  way  tubercle  bacilli  which  have  passed  through 
many  generations  in  the  bodies  of  herbivora  become  as  it  were  accli- 
mated, and  are  best  able  to  infect  again  an  animal  of  the  same  species. 
The  tubercle  bacilli  of  birds  (whose  normal  body  temperature  is 
known  to  be  41° -42°  C,  and  whose  tissues  and  fluids  from  their 
known  resistance  to  tetanus  virus,  etc.,  must  have  totally  different 
affinities  from  those  of  mammals)  are  particularly  changed  in  their 
biological  characteristics  so  that  thev  seem  to  be  of  a  totallv  different 
stock ;  and,  too,  it  is  difficult  to  successfully  induce  a  growth  of 
tubercle  bacilli  from  mammals  in  the  avian  body.  However,  now 
and  again  birds  have  been  rendered  typically  tuberculous  by  inocu- 
lation with  mammalian  tuberculosis,  and  conversely  horses  (No- 
card)  have  been  infected  with  avian  tuberculosis;  and  therefore  the 
differences  may  be  considered  as  merely  expressions  of  a  varia- 
bility of  biological  properties.  We  must  consider  tuberculosis  of 
man  and  the  animals  as  caused  by  one  and  the  sanie  infectious 
agency,  zvhich  from  long  transmission  througJi  one  particular  animal 
species  may  develop  definite  varieties  and  strains  of  uneven  patho- 
genic pozi'cr.  (For  further  details  consult  Xocard-Leclainche :  Les 
Maladies  Microbiennes  des  Aniinau.v.     III.  Ed..  Paris,   1903.) 

The  anatomical  lesions  determined  by  the  tubercle  bacillus  are 
as  follows :  After  being  conveyed  into  the  body  of  a  man  or  ani- 
mal the  tubercle  bacillus  multiplies  into  masses,  provided  it  finds  a 
suitable  soil  at  the  temperature  of  the'  animal ;  penetrates  by  growth 
into   the    tissues    and    is    carried    more    widely   by   the    wandering 


Tuberculosis. 


299 


cells.  Its  deposition,  along  with  the  toxine  which  it  produces, 
causes  a  reaction  on  the  part  of  the  tissue  as  about  a  foreign 
body,  in  which,  however,  the  special  toxic  action  of  the  micro- 
organism takes  part  and  gives  rise  to  coagulation  necrosis. 
The    first    evidence    of    reaction    as    shown    by    the    studies    of 


EmboL_    . 

cheesy  centre 
tissue ;    X    00 


Vlg.    02. 

lie  miliary  tubercle  from  lung  of  liorse  (after  Johne)  ;  a.  giant  cells:  h, 
lieesy  centre:  r,  small  as  yet  not  caseated  tubercle;  cl,  surrounding  pulnionai-y 
issue ;    X    00. 

Baumgarten,  Johne  and  others  is  the  appearance  of  karyokinetic 
figures  in  the  fixed  connective  tissue  cells  and  endothelial  cells, 
and  side  by  side  with  this  an  increase  of  the  latter.  The  prolifer- 
ating fibroblasts,  among  which  usually  giant  cells  occur,  surround 


the    tubercle    bacilli ;     and     further     out 


immigrating    leucocytes 


300  Specific  Inflammations. 

or  lymphocytes  collect  about  the  periphery  of  the  focus  occupied 
by  the  bacilli.  In  this  manner  a  rounded  cellular  nodule  is 
formed,  at  first  microscopic  in  size,  but  later  increasing  in  bulk  to 
that  of  the  head  of  a  pin  or  millet  seed,  and  known  when  visible 
to  the  naked  eye  as  a  suhmiliary  and  miliary  tubercle  (niilium,  a 
millet  seed).  It  is  of  a  gray,  opal-glass-like  color,  with  a  dead-white 
to  yellowish  point  in  the  centre  which  indicates  the  early  stage  of 
coagulation  necrosis    (caseation).      [The  central  cells  of  the  unde- 


••;-      'fa^sSv-iix  ,    .     y^^,-'  r^iji ;::<'•' 


Fig.    UJ. 

Miliary   tubercle    (higher  magnification):   a,   giant   cell:   b.   caseated   centre;   c,   zone 
of  epithelioid  cells  ;  d,  zone  of  lymphoid  cells. 

generated  miliary  tubercle,  in  and  among  which  the  tubercle  bacilli 
are  found,  are  of  uncertain  origin.  They  are  commonly  spoken  of 
as  endothelioid  or  epithelioid  from  the  comparatively  large  amount 
of  protoplasm  and  the  rather  pale  and  vesicular  nucleus,  and  are 
distinguishable  by  these  features  from  the  ordinary  fibroblasts.  They 
vary  in  shape  but  are  more  commonly  of  a  rather  flattened  spindle 
form  than  otherwise.  The  author's  view  that  these  are  essentially 
the  same  as  young  connective  tissue  corpuscles  and  tlie  product  of 
proliferation  of  the  fixed  connective  tissue  cells  is  accepted  by  some; 


Tuberculosis. 


301 


others  believe,  as  the  name  endotheHoid  would  suggest  (epithehoid 
synonymous  and  used  rather  to  indicate  the  general  epithelial-like 
appearance  than  referring  to  the  source  of  these  elements), 
that  they  are  derived  from  the  endothelial  cells,  mainlv  those  of  the 
lymph  spaces  in  which  the  bacilli  are  lodged.  The  true  lympho- 
cytic nature  and  origin  of  the  peripheral  zone  of  small  mono- 
nuclear cells  is  commonly  accepted.  There  is  considerable  uncer- 
tainty as  to  the  mode  of  formation  of  the  giant  cells.  According  to 
some  they  are  the  result  of  the  fusion  of  cells  undergoing  hyaline 
or  coagulative  change ;  and  are  therefore  looked  upon  by  these  per- 
sons as  evidence  of  beginning  or  advancing  degeneration  in  the 
focus.  From  this  standpoint  a  miliary  tubercle  when  exhibiting  one 
or  more  giant  cells  in  its  structure  is  essentially  a  degenerating 
tubercle.  Others  believe  that  they  are  the  result  of  inefficient  proto- 
plasmic division  of  growing  cells,  in  other  words  are  of  a  prolif- 
erative type  of  development  and  not  of  the  significance  just  indi- 
cated. Tubercles  of  fresh  and  undegenerated  structure  are  com- 
monly called  gray  tubercles ;  older  and  degenerated  ones,  yellow 
tubercles.  | 

The  site  of  formation  of  the  tubercle  is  in  the  connective  tissue 
framework  of  the  affected  part  or  in  the  walls  of  the  blood  vessels 
and  in  the  lymphatic  foci  of  die  tissue.  This  gives  the  cellular  pro- 
liferation a  connective  tissue  frame  work  or  reticulum  as  a  skeleton, 
which  may,  however,  be  in  part,  too,  a  product  of  the  fibroblasts 
and  giant  cells,  which  of  course  also  supply  an  intercellular  sub- 
stance. Although  endothelial  cells  also  take  part  in  the  formation 
of  the  cellular  nodule  these  do  not  develop  into  vascular  buds,  and 
the  miliary  tubercle  is  avascular.  The  endothelial  cells  in  their  pro- 
liferation may  occlude  the  lumen  of  the  capillary  vessels ;  and  more- 
over by  the  growth  of  the  cellular  mass  the  vessels  may  be  com- 
pressed. In  contrast  to  these  factors  the  tuberculous  reaction  may 
also  present  itself  as  a  dift'use  proliferation,  without  production  of 
sharply  defined  nodules  and  with  the  formation  of  new  blood  ves- 
sels. In  this  case  there  is  found  a  soft,  gray  or  grayish  red  layer, 
especially  seen  in  serous  surfaces  (bovine  heart),  which  is  not  likely 
to  undergo  more  than  a  slight  caseation,  or.  if  it  does,  only  after 
considerable  time.  This,  too,  always  has  a  distinct  granular  appear- 
ance looking  as  if  caused  by  fusion  of  closely  set  miliary  tubercles. 
This  diffuse  growth  is  due  to  the  fact  that  separate  groups  of  tuber- 
cle bacilli  do  not  here  occur  as  the  centres  of  nodular  circumscribed 
cellular  collections,  but  that  large  numbers  of  the  organisms  are 
scattered  all  through  the  tissue. 


302 


specific  I)if!aiiiinatioiis. 


This  inflammatory  reaction  is  not  characterized  merely  by  the 
marked  collection  of  wandering  cells  in  the  tuberculous  tissue,  but 
also  by  actual  exudation  upon  the  surfaces  of  the  organs.  Especially 
in  the  pleural  cavity  of  dogs  tliis  may  be  seen  as  a  marked  sero-cel- 
lular  collection  of  fluid,  the  result  of  a  purely  tuberculous  granula- 
tion ;  and  in  various  tuberculous  tissues  microscopic  examination 
shows  the  appearance  of  thread-like    (fibrinoid,  Schmauss  and  Al- 


Fig.   64. 

Miliary   tubercle   in   the   liver  of  a    dog    (slightly   magnified). 


brecht)  coagulation  masses  lying  between  the  proliferating  and  de- 
generating cells  and  suggesting  an  exudative  origin. 

With  the  proliferation  of  the  tubercle  bacilli  and  their  extension 
into  the  adjacent  tissues  the  amount  of  toxic  material  given  of¥ 
by  them  and  taken  up  by  the  lymph  becomes  increased.  The  casea- 
tion is  to  be  ascribed  to  the  influence  of  this  substance ;  and  in  pro- 
portion to  the  latter  the  caseous  areas  grow'  larger  as  the  reactive 
cell  proliferation  increases  the  size  of  the  nodule.  At  first  puncti- 
form  or  streaked  cloudy  specks  appear  and  the  necrotic  foci  fuse 
into  progressively  larger  and  larger,  dry,  anaemic  or  (after  a  fatty 


Tiiherciilosis. 


303 


disintegration)  into  soft,  partly  purulent,  partly  caseous  areas  of 
very  variable  size.  Such  necrosed  parts  may  become  impregnated 
with  lime  salts  (especially  in  cattle)  and  eventually  assume  a 
chalky,  plaster-like  or  sandy  appearance. 

Just  as  in  chronic  productive  inflammation  the  fibr()])]astic  tissue 
is  changed  into  a  firm  cicatricial  mass,  the  proliferated  connective 
tissue  cells  of  a  tubercle  are  also  able  to  assume  a  genuine  fibro- 


Fig.    65. 
Funguus   tubercle   with   giant   cells    (without   caseatiou)    from   the   larynx  of  a   cow. 


plastic  function,  particularly  in  the  formation  of  a  fibrillar  matrix 
and  may  thus  give  to  the  tubercle  a  firm  fibrous  character. 

It  may  therefore  be  appreciated  that  the  anatomical  forms  of 
tuberculosis  vary  considerably  according  to  the  tissue  predisposition 
in  the  diiTerent  animal  species,  and  the  extent  and  duration  of  the 
process.  The  principal  forms  are:  miliary  tuberculosis,  tubercu- 
lous ulceration,  tuberculous  cheesy  infiltration,  tuberculous  cavities, 
■fungous  granulontatons  tuberculosis   (or  tuberculoma). 

The  miliary  tubercle,  the  earliest  product  of  the  reactive  process 
of  the  disease,  as  already  stated,  appears  as  a  gray  or  yellowish-red 


304 


Specific  Inflammations. 


nodule  of  the  size  of  a  pin  head  or  millet  seed ;  these  may  be  single 
or  multiple,  may  be  scattered  widely  over  a  large  surface  and  dis- 
seminated in  the  same  way  throughout  the  organic  substance,  par- 


Fig.   66. 


Tuberculosis    of    liver    of    a    pheasant.     The    tubercles    show   a    sharp    limitation    of 

the  cheesy  centres. 


Fig.    67. 

Tuberculosis    of    liver    of   dog.      (After    Cadiot.) 


ticularly  on  serous  surfaces  and  in  the  lungs.  They  develop  to  visible 
size  within  from  fourteen  to  thirty  days  after  infection ;  the  micro- 
scopic stages  at  the  very  beginning  may  be  made  out  as  early  as 
from  five  to  ten  days.     If  the  organ  is  the  seat  of  submiliary  or 


Tuberculosis. 


305 


miliary  nodules  alone,  all  of  the  same  age,  that  is  of  uniform  size, 
it  is  said  to  be  involved  by  acute  miliary  tuberculosis.  With  local 
multiplication  of  the  tubercle  bacilli,  the  nodules  enlarge  to  the  size 
of  a  lentil,  pea  or  nut,  these  larger  forms  usually  showing  their 
origin  from  fusion  or  conglomeration  of  smaller  miliary  tubercles. 
This  condition  constitutes  what  is  known  as  chronic  miliary  tubercu- 
losis. On  serous  surfaces  the  formation  of  nodular  masses  gives 
rise  to  the  so-called  pearl  disease. 

The  tuberculous  fungous  granuloma  is  the  result  of  a  progres- 
sive formation  of  cellular  nodules  and  their  profuse  growth  on  free 

surfaces;    it    is    chiefly    met    with     in . — _^ 

the  thoracic  serous  membranes  and 
peritoneum  and  sometimes,  too,  in 
the  intestinal  nmcous  membrane.  By 
the  synchronous  development  of  the 
nodules  and  of  a  vascular  connective 
tissue  growth,  there  may  be  produced 
ofravish-white,  gravish-red  and  yellow- 
ish-red  tumor-like  masses  from  the  size 
of  an  egg  to  that  of  a  fist,  which  are 
piled  up  about  and  over  each  other  as 
large  excrescences,  covering  consider- 
able surface  areas  and  reaching  per- 
haps a  weight  of  from  twenty  to  forty 
kilogrammes.  Caseation  of  these  tu- 
berculomata,  which  also  occasion  adhe- 
sions of  the  serous  surfaces,  at  first 
appears  in  punctiform  foci  and  in 
small  spots  in  the  granulation  tissue, 
as  yellow  or  light  yellow  opacities,  and 
can  advance  to  complete  transforma- 
tion of  the  whole  bunch  of  nodules  into 
a  mass  which  on  section  looks  like  corn-bread,  yellow,  hard,  gritty 
and  partly  calcified. 

Tuberculous  ulcers,  especially  in  the  bowel,  larynx  and  bron- 
chial tree,  result  from  the  maceration  and  disintegration  of  the 
caseated  parts  as  well  as  from  a  purulent  softening  of  the  tuber- 
cles developing  in  the  mucous  surfaces  (lymph  follicles).  These 
areas  of  tissue  destruction  are  circular  or  oblong,  shallow  or  some- 
times a  millimeter  in  depth,  as  large  as  a  lentil  to  a  little  over  a 
centimeter  in  diameter,  or  in  the  bowel  reaching  perhaps  the  length 
of  a  finger  and  two  fingers  in  breadth.    The  base  of  the  eroded  spot 


Figr.  68. 

Ulcerative  tuberculosis  of  intes- 
tine of  cow.  (Mucous  sur- 
face of  small  intestine.) 


3o6 


Specific  Inflauiuiations. 


is  mottled  grayish-red  and  yellowish,  and  minute  tubercles  can  be 
distinguished  growing  on  the  base  and  margins  of  the  ulcer.  The 
base  looks  granulated;  the  bordering  wall  of  mucous  membrane  is 
thickened  and  sometimes  a  marginal  circlet  of  projecting  miliary 
tubercles  can  be  seen  about  it. 


Fig.   69. 
Chronic  miliary  tuberculo.sis  and  lobular  tuberculosis  of  lung  of  horse. 

Cheesy  tuberculous  i)ifiltration,  apt  to  be  found  involving  Ivmph 
nodes  or  lungs,  changes  the  affected  area  of  the  organ  into  a  very 
large,  hard,  densely  caseated  mass  of  a  yellowish  white  to  chrome 
yellow  color,  reminding  one  much  of  the  boiled  yolk  of  an  egg. 
This  change  is  apt  to  be  very  diffuse  and  is  generallv  accompanied 


Tuberculosis. 


307 


^\ 


'^,. 


by  the  formation  of  a  firm  bacony  connective  tissue  of  the  nature 

of    a    confluence    of    fibrous    tubercles,    or    in    other     words    a 

chronic    tuberculous    inflammation.      Lymph    glands,    the    seat    of 

tuberculous  infiltration,  may  grow  to  enormous 

masses  as  thick  as  an  arm,  or  the  size  of  loaves  of 

bread.   .Bunches  of  tuberculous  pulmonary  lobules 

are   converted   into   dry   necrotic  masses   as   big 

as  a  fist  and  comparable  in  appearance  to  Edam 

cheese    or    Swiss    cheese ;    or    sometimes    whole 

lobes   are   changed   into    large,    lumpy    masses, 

hard,    weighing   over    a    kilogram,    and    riddled 

with  points  of  cheesy  softening. 

Tuberculous  an'ities,  developing  in  the 
areas  of  cheesy  infiltration,  are  cavities  varying 
from  the  size  of  a  nut  or  fist  to  a  span  [a  span  is 
nine  inches]  and  a  half  in  diameter.  They  con- 
tain a  greasy,  caseous  and  slimy  mass  of  detritus 
and  are  limited  by  a  wall  of  pale,  indurated 
fibrous  tissue  or  by  the  tissue  of  the  organ  modi- 
fied by  the  dift'erent  color  shades  given  by  the 
tuberculous  inflammation.,  and  giving  rise  to  the 
cavities    by    degenerative    changes    affecting    it. 

These  more  important  types  of  tuberculous 
changes*  may  combine  in  various  ways  anil 
there  are  apt  to  be,  too,  special  modifications  due 
to  peculiarities  of  the  tissues  in  the  various  types 
of  animals.  While  cheesy  areas  in  cattle  usually 
have  an  intense  yellow  color,  in  horses  and  car- 
nivora  they  are  apt  to  be  whiter  and  sometimes 
quite  milky.  They  are  not  at  all  uniform  in 
consistence,  sometimes  dry  and  cheesy,  some- 
times soft  and  pultaceous  or  possibly  broken 
down  into  a  pus-like  fluid.  Caseation  may  in 
some  instances  be  absent  and  the  tubercles 
may  be  of.  a  more  cellular  character,  look- 
ing like  the  tissue  of  lymph  glands ;  or  they  may  become  hard 
and  fibrous   (in  horse). 

The  entrance  of  tubercle  bacilli  into  a  tissue  generally  occurring 
at  places  where  lymph  nodes  He  exposed  (pharynx,  intestine)  at  first 
causes  a  primary  local  tuberculosis  at  the  point  of  infection.    How- 

*Foi-  detailed  examples  cf.  KUt,  LcIiiIiikIi  d.  iii>c.~.  imtli.  Aunt.,  11.  .\iitl., 
Stuttgrart,   100.'?.     F.   Enke. 


'■-i 


Fig.    70. 

'riiherculoiis  rib  of 
cow  (fresli  sec- 
tion). 


3o8 


Specific  Inflammations. 


ever  the  point  of  infection  may  escape  involvement  provided  the 
tubercle  bacilli  are  rapidly  carried  onward  by  the  lymph,  under 
which  circumstances  the  tuberculous  inflammation  may  first  show 
itself  in  the  lymph  glands.  After  feeding  tuberculous  material  to 
hogs  the  mucous  membrane  of  the  intestine  is  uniformly  unaffected 
and  the  disease  primarily  occurs  in  the  mesenteric  lymph  nodes. 
[Ravenel  has  produced  a  similar  primary  involvement  of  the  lymph 
nodes  of  the  mesentery  in  dogs  by  feeding  the  tubercle  bacilli 
rubbed  up  in  butter,  having  previously  starved  the  experiment  ani- 
mal for  a  time.]  After  being  taken  up  by  the  chylous  vessels  the 
tuberculous  virus  passes  into  the  blood  by  way  of  the  thoracic  duct 
and  thence  into  the  lungs,  and  after  traversing  the  lesser  circulation 
is  carried  to  all  of  the  organs.   The  different  organs  do  not  all  show 


wm^^ 


Fig.  71. 
Portion    of    lung   of   horse    showing   miliary    tubercles    and    tuberculous    infiltration. 


a  uniform  predisposition  to  the  influences  of  the  bacilli,  that  is, 
they  do  not  all  offer  equally  favorable  conditions  for  the  nutrition 
of  the  microorganisms.  The  lungs,  lymph  glands  and  especially  the 
general  lymphatic  tissues  (bone-marrow,  spleen),  are  places  where 
the  bacillus  most  readily  lodges.  For  this  reason  the  lungs  may 
become  the  seat  of  the  primary  involvement  after  feeding  tubercle 
bacilli  to  an  animal,  and  the  existence  of  the  pulmonary  afifection 
is  by  no  means  to  be  looked  upon  as  indicating  that  infection  took 
place  by  inhalation. 

The  primary,  and  in  fact  the  only  tuberculous  focus  may  be  en- 
countered in  the  interior  of  bones,  or  in  lymph  glands  or  the  tes- 
ticle. In  such  instances  isolated  tubercle  bacilli  which  have  gained 
access  to  the  blood  may  have  been  caught  and  lodged  in  any  such 


Tuberculosis. 


309 


situation  and  there  caused  the  disease.  Generally  the  whole 
path  traversed  hy  the  l)acilli  is  mapped  out  l)y  foci  of  the 
disease,  first  the  primary  local  focus  and  after  it  the  neighl^oring 
regional  infection,  then  the  secondary  tuberculosis  of  the  lymph 
glands  which  receive  the  lymph  from  the  afifected  part.  From  the 
latter  along  the  lymphatics  or,  as  above  mentioned,  by  the  chylous 
route,  the  germs  find  their  way  into  the  blood  or  may  directly  pene- 
trate through  the  walls  of  the  blood  vessels  in  the  course  of  the  tu- 
berculous proliferation  ;  and  then,  depending  upon  whether  many  or 
only  isolated  bacilli  are  carried  to  the  various  organs,  there  is  pro- 


Uteriiit^  tuliorcuUisis,  from  cow. 


duced  a  iiictastafic,  hccmafogciifliis,  embolic,  multiple  or  dissemi- 
nated miliary  tuberculosis  of  the  lungs,  brain,  liver,  kidneys,  etc. 
Muscle  (meat)  shows  the  greatest  degree  of  resistance,  usually  only 
the  intermuscular  lymph  nodes  being  affected.  This  general  inva- 
sion of  the  tuberculous  virus  with  its  resulting  tuberculous  foci  is 
spoken  of  as  general  tuberculosis.  The  metastatic  miliary  nodules 
of  course  increase  in  size,  and  by  confluence  and  advancing  casea- 
tion cause  progressive  extension  of  the  tuberculous  destructive 
changes.  Finally,  too,  contact  infection  along  mucous  membranes 
occurs  from  the  convection  of  the  germs  over  the  surface  with  its 
fluid  secretion,  as  infection  of  the  larynx  from  the  lungs,  of  the 
vulva    from   the  uterus,   etc. 


310  Specific  Iiiflaniniations. 

The  symptoms  of  tuberculosis  appreciable  during  the  hfe  of  the 
affected  animal  vary  widely  with  the  different  situations  of  the  pri- 
mary disease.     Fuller  details  than  space  here  permits  are  contained 
in  the  publications  of  Johne,  Siedamgrotzky,  Albrecht,  Lydtin  and 
other  authors  and  particularly  the  text  books  of  Friedberger  and 
Frohner,  Dieckerhoff,     Csokor,     Nocard-Leclainche    and     AIoussu. 
Pulmonary  tuberculosis  manifests    itself    by  a  remittent  fever,  im- 
paired condition  of  nutrition  in  spite  of  good  appetite,  induration 
of   the   skin    (hide   binding)    associated   with   loss  of   subcutaneous 
fat,  rapid  and  difficult  breathing,  a  feeble  dry  cough,  impairment  of 
percussion  resonance  and  the  presence  of  rales.     Chronic  tiatulence, 
as  pointed  out  by  Johne,  is  a  frequent  evidence  of  the  existence  of 
greatly  enlarged  tuberculous  mediastinal  lymph  glands  from  pres- 
sure   on    the    gullet,    interfering    with    belching.     Tuberculosis    of 
the  mammary  gland  may  be  recognized  by  a  gradually  increasing 
induration  and  diffuse  painless  swelling  in  one,  two  or  all  parts  of 
the   udder,    with    synchronous   enlargement   of   the   supramammary 
lymph  nodes.     In  this  condition  the  milk  may  be  quite  normal  in 
appearance    for    weeks    or    at    least    only    changed     in    that     it 
is  more  watery,  thinner  (in  the  last  stages  only  may  one  notice  the 
admixture  of  small   fiakes  of  a  pus-like  appearance).     Superficial 
lymphatic  glands,  as  the  retropharyngeal,  often  become  very  large 
in  tuberculosis,  hard  and  nodular.     Tuberculosis  of  the  brain  com- 
monly shows  the  violent  symptoms  of  meningitis   (excitement,  un- 
consciousness).    In  tuberculosis  of  the  ovary  symp.^toms  of  sexual 
desire  are  sometimes  observed.     Tuberculosis  of  serous  membranes 
can  in   some  cases  only  be  made  out  by  the  detection  of  friction 
sounds  or  by  palpation  of  the  peritoneum  through  the  rectum ;  it 
may  exist  extensively  without  the  occurrence  of  any  emaciation  of 
the  animal   (so-called  "fat  Frenchmen"),  but  on  the  contrary  with 
preservation  of  an  excellent  state  of  nutrition.     In  the  same  way 
involvement  of  the  deeper  lymph  glands,  liver  and  intestine  is  apt 
to  escape  diagnosis  during  life. 

Diagnosis  can  be  positively  confirmed  by  the  microscopic  exam- 
ination of  the  various  emanations  (milk,  vaginal  discharge,  bron- 
chial mucus,  etc.)   by  determination  of  the  tubercle  bacilli  therein. 

As  a  valuable  aid  to  diagnosis  especially  in  the  latent  forms  of 
the  disease,  the  use  of  luberculin  may  be  approved ;  this  is  a  decoc- 
tion of  cultures  of  the  tubercle  bacillus  [sterilized  by  filtration 
through  porcelain]  which  has  the  effect  of  causing  a  febrile 
reaction  in  tuberculous  subjects,  non-tuberculous  individuals,  how- 
ever, manifesting  no  reaction  to  similar  doses  of  the  material. 


danders.  31 1 

Tuberculosis  can  be  successfully  coniljuted  as  purely  conta- 
gious-infectious disease  by  regulations  contemplating  required  dis- 
infection of  all  effluvia  containing  tubercle  bacilli.  Recently  a 
.metbod  of  protective  inoculation  of  cattle  against  tuberculosis  bas 
been  discovered  by  v.  Behring,  immunizing  the  animals  by  means 
of  strains  of  tubercle  bacilli  of  low  virulence.  [Dixon  in  1889 
found  that  he  obtained  resistance  in  rabbits  against  virulent  bovine 
bacilli  after  having  previously  inoculated  them  with  material  from 
an  old  laboratory  culture  containing  club-shaped  and  branching 
forms.  It  is  of  interest,  too,  that  successful  vaccination  of  cattle 
against  virulent  bovine  tuberculosis  has  been  practiced  by  Pearson 
in  this  country,  using  cultures  of  human  tubercle  bacilli  of  low 
virulence.  I  Cows  which  have  obtained  a  high  degree  of  immuniza- 
tion produce  milk  which  possesses  a  certain  amount  of  immunizing 
bodies ;  and  it  may  be  hoped  that  either  by  using  such  milk  or  the 
serum  of  highly  immunized  animals  there  may  be  obtained  aho  a 
curative  method  for  consumption  in  man. 

Glanders. 

Glanders  (mallcosis)  is  a  contagious  disease  caused  by  the  glan- 
ders bacillus  {bacillus  mallei),  occurring  in  the  horse,  ass  and  mule, 
but  very  infectious  and  dangerous,  to  man  and  also  transmissible  to 
carnivora,  sheep,  goat,  guinea-pig,  liAlge-hog,  field-mouse,  rabbit 
and  camel.  The  cow  is  entirely  immune  even  after  every  effort  at 
inoculation ;  and  the  hog  can  be  infected  only  with  considerable  dif- 
ficulty; domestic  fowls  are  also  immune. 

This  infectious  malady  causes  both  in  its  acute  and  chronic  course 
(the  latter,  perhaps  persisting  for  years)  a  purulent  fibroplastic  in- 
flammatory change,  developing  mainly  in  the  skin  and  respiratory 
mucous  membranes.  Pathological  changes  also  invariably  occur  in 
the  lymph  vessels  and  lymphatic  glands ;  and  in  addition  metastatic 
foci  may  follow  in  the  spleen,  liver,  testicles,  kidneys,  sometimes  in 
the  flesh,  and  finally  a  general  blood  infection  results. 

The  microorganism  of  the  disease,  the  glanders  bacillus,  discov- 
ered by  Schiitz  and  Loeffler,  is  always  present  in  all  tissues  the  seat 
of  glanders  changes,  in  the  discharges  of  the  subject  mixed  with 
glanders  pus.  and  is  sometimes  found  in  the  blood.  It  is  a  short  rod- 
shaped  organism,  measuring  from  two  to  five  micromillimeters  in 
length  and  from  one-half  to  one  micromillimeter  in  width.  It  does 
not  exist  free  in  nature,  but  multiplies  •  exclusively  in  the  animal 
body  (cf.   contagions  diseases,  p.  yx)  ;  only  under  special  conditions 


312  specific  Inilammations. 

can  it  be  grown*   in   the  incubator  on  nutrient  media    (glycerine 
bouillon,  serum,  agar,  potatoes). 

Transmission  of  the  infectious  agents  from  one  animal  to  an- 
other or  to  man  is  the  result  of  a  close  relationship  (living  together) 
or  actual  contact  of  the  diseased  animals  with  others ;  and  may  take 
place  when  the  vehicle  of  the  contagion  (pus,  nasal  discharge,  etc.) 
gets  upon  the  fodder  and  in  the  water,  or  when  discharged  in  cough- 
ing or  blown  out  in  sprays  of  fine  drop- 
^       js  ^  lets   and   iniialed   by  other  animals.     If 

*       \  «         ^  the   material    should   lodge   on  the   skin 

\-' 
\  ^   ''\'  N        and    mucous    membranes    it    may    pene- 

Jfvv*  \           "trate    even    through    apparently    intact 

"^  pores   (transmission  by  blankets,  saddles 

^                 .  •  and  harness  soiled  with  the  pus).     Ar- 

1  tificially  the  disease  may  be  reproduced 

*     /  f-T       '-'-^     cutaneous,    subcutaneous,    intraperi- 

i     ^  toneal   and  other   forms   of   inoculation. 

Fig.  73.  and   by    feeding  the  glanders   germs   to 

Glanders    bacilli    (from    cui-     the  susceptible  animals.      From  the  ex- 

ture). 

permiental  studies  of  Nocard  and 
Leclainche,  Galtier,  Conte,  Renault,  Cadear  and  Malet,  the 
smallest  lesion  of  the  epithelium  in  mucous  membranes 
may  serve  as  a  point  of  entrance  for  the  germ,  as  the  trivial  lesion 
which  is  produced  by  rubbing  with  a  piece  of  linen  cloth  or  the 
tiny  epithelial  abrasions  about  the  nostrils  caused  by  bits  of  food- 
stuff. In  guinea-pigs  the  infection  may  be  successfully  produced  by 
dropping  the  glanders  bacilli  into  the  conjunctival  sac  upon  the  in- 
tact mucous  surface,  probably  through  the  lymph  follicles  and  tear 
ducts.  In  feeding  experiments  the  lymph-follicles  of  the  pharnyx 
and  intestine  are  the  points  of  entrance  of  the  infection.  Inhala- 
tion of  tlie  germs  distributed  by  spraying  also  occasions  infection  of 
the  pharyngeal  mucous  membrane.  The  infection  develops  most 
rapidly  after  intravenous  and  intracranial  injection. 

The  bacilli  multiply  at  first  locally  upon  and  within  the  tissue 
(lymph  spaces,  lymph  follicles)  to  which  they  have  gained  access, 
and  produce  by  the  influence  of  their  metabolic  products  a  progres- 
sive cellular  necrosis  with  destruction  of  the  nuclei  (formation  of 
granules  and  globules,  fragmentation  of  chromatin)  and  trans- 
formation of  the  cells  into  finely  granular  detritus.  Coincidentlv 
tliere  is  seen  a  continual  emigration  of  the  white  blood  corpuscles, 

*  For    details    cf.    Kitt,    Bakterienkundc   fur    Tlerarxtc.     IV    Aufl.,  Wien.    1903 


Glanders. 


313 


that  is.  a  local  inflammation,  which  in  the  chronic  form  of  the  affec- 
tion also  produces  a  wall  of  demarcation  by  fibroblasts.  With 
the  persistent   and  progressive  multiplication  of  the  bacilli   in  the 


Fig.   74. 
Microscopic   section    through   a   glanders  nodnle   in    hmg  of  horse. 


Fig    75. 
Glanders  nodules,  erosions  and  ulcers  of  the  nasal  septum  of  horse. 

inflamed  and  necrobiotic  tissue,,  this  limiting  new  tissue  is,  however, 
continuallv  being  broken  down  and  the  area  of  destruction  is 
widened.  '  The  virus  being  taken  up  by  the  leucocytes,  multiplying 


314 


Specific  Inflammations. 


mmm^^W} 


in  the  lymph  spaces  and  therefore  open  to  lymph  convection,  is  dis- 
seminated in  the  vicinity  of  the  primary  focus,  passes  along  the 
lymph  vessels  and  into  the  blood ;  and  new  points  of  deposition  and 
new  foci  of  the  disease  occur  locally  and  metastatically.  The  bacilli 
are  also  carried  by  currents  of  secretion  and  may  lodge  in  a  fresh 
position  on  the  mucous  membrane,  here  again  to  give  rise  to  new 
colonies,  as  where  they  are  carried  from  the  lungs  to  the  larynx 

and  pharynx.  The  metabolic  prod- 
ucts of  the  organisms,  developing  in 
the  system,  by  their  toxic  influences 
occasion  fever  and  wasting. 

The  visible  anatomical  changes 
of  the  disease  vary  considerably  with 
the  virulence  of  the  affection  and  the 
tissue  predisposition  of  the  particu- 
lar kind  of  animal.  The  principal 
types  are  the  glanders  nodules, 
glanders  abscesses,  gla)iders  indu- 
rations and  glanders  infiltrations. 

Glanders  nodules,  developing 
niainl}-  in  the  lungs  and  parenchyma- 
tous organs,  appear  as  grayish-white, 
semitransparent.  opalescent,  rounded 
])rominences  or  deposits  ranging  from 
the  size  of  a  grain  of  sand  to  that 
of  a  pea,  their  central  portion  break- 
ing down  into  a  yellowish-gray, 
purulent  or  dry  cheesy  material.  In 
the  lung  they  are  often  surrounded 
by  a  dark  red  area.  The  glanders 
ulcers  present  themselves  on  the  mu- 
cous membranes  of  the  respiratory 
tract  as  shallow  or  deep  lesions,  varying  from  the  size  of  a  lentil 
to  that  of  a  silver  dollar ;  the  loss  of  substance  giving  the  mucous 
membrane  an  appearance  of  being  eaten  or  gnawed.  The  larger 
ones  have  thick,  wall-like,  eroded  margins.  These  ulcers  have  a 
bacon-like  gray  color,  with  the  bordering  mucous  membrane  often 
dark  red  and  hyperaemic,  bleeding  on  the  least  provocation.  There 
are  usually  large  numbers  upon  an  affected  mucous  membrane. 
The  glanders  ulcers  of  the  skin  range  from  the  size  of  a  lentil  to 
that  of  a  half  dollar,  are  of  a  dirty  grayish-red  color,  covered  with 


Fig.    76. 

Glanders   induration   of  the   uasal 

mucous    memibrane    of    tbe 

horse. 


Glanders. 


315 


pus  and  half  dried  crusts,  and  (he  surrounding  hairs  are  soiled  with 
pus.  These  ulcers  often  undenuine  the  skin  producing  crater-like 
openings  (like  the  anus  of  a  chicken)  and  are  apt  to.be  found  in 
rows  one  after  another  and  alongside  of  each  other. 

Glanders  abscesses  are  commonly  found  in  the  skin  as  some- 
what rounded  boils  of  the  size  of  a  hazel  nut  or  a  walnut,  with  the 
hair  lost  from  over  their  surface.  They  fluctuate  and  contain  a 
thin,  oily,  yellow  or  yellowish-red  pus,  sometimes  a  rather  thick  and 
mushy  detritus,  and  their  wall  is  made  up  of  bacony,  eroded  cutis 


Fig.   77. 
Glanders    uodules    and    iudurations    of    lung    (;f    horse.      Natural    size. 


and  induration  tissue.  They  are  apt  to  be  found  in  rows  enclosed 
in  the  swollen,  dense  lymphatic  cords  ;  that  is  they  form  foci  of  sup- 
puration interrupting  the  lymph  vessels  like  a  rosary. 

Glanders  Uidurations  occur  on  mucous  membranes  as  the  result 
of  a  demarcating  fibroplastic  proliferation  in  the  form  of  solid,  nod- 
ular or  ridge-like,  thick  prominences  of  the  mucous  membrane,  with 
a  yellowish-gray  to  reddish-yellow  color,  and  a  smooth  slippery  sur- 
face. These  thickenings  may  appear  as  isolated  prominences  of  the 
size  of  a  hemp  seed  or  oat  seed,  or  may  be  fused  so  as  to  form  hard 
stellate  and  radiating  scars  like  frost-cr\stals.  not  extending  deeply. 


3i6 


Specific  Inflammations. 


and  projecting-  somewhat  above  the  surface.  They  are  scattered  all 
over  the  surface  of  the  mucous  membrane,  often  in  large  numbers, 
and  may  sometimes  occur  in  rows.  Sometimes  this  chronic  indura- 
tive inflammation  may  form  patches  of  thickening  a  finger's  length 
in  extent  and  several  centimeters  broad,  standing  out  like  cushions 
in  marked  relief,  sometimes  of  dull  grayish-yellow  color  or  mottled 
with  bright  red  points,  and  their  smooth  surface  covered  with  a 
viscid  pus.  Occasionally  warty,  soft,  raspberry-colored,  projecting 
granulations  are  found  grow'ing  from  the  mucous  membranes. 
In  the  lungs  indurative  patches  are  met  sometimes  about  suppu- 


Fig.  78. 
<;iander.s   nhscesses   of   the   skin    (jf   horse. 


(Photographed    by    Dr.    Jakob.) 


rating  and  caseating  glanders  nodules  as  bacony,  grayish-white 
zones  of  demarcating  tissue,  sending  radiations  into  the  pulmo- 
nary tissue;  sometimes  as  broad  yellowish-white,  poorly  defined 
areas  of  connective  tissue,  merging  into  the  pulmonary  structure, 
involving  numerous  lobules  and  changing  them  into  a  dense  mass, 
and  cutting  with  a  tough,  leathery  resistance.  On  the  inside  of  such 
areas  are  met  dull  yellow,  ochre-colored,  moist  cheesy  or  dry 
plaster-like  deposits. 

Glanders  infiltrations  develop  in  the  lung  as  true  pneumonias  of 
catarrhal,  suppurative  or  croupous  types,  and  as  a  sclerosing  form ; 
tlie  former  in  acute,  the  latter  in  chronic  glanders.     Especiallv  in 


Glanders. 


317 


the  cat  family  the  hing's  arc  involved  just  as  in  croupous  pneumonia 
and  show  stages  of  red  and  gray  hepatization.  In  the  horse  the 
lungs  are  apt  to  show  a  confused  mixture  of  inflammatory  changes ; 
groups  of  lobules  are  found  all  through  the  lungs  forming  wedge- 
shaped,  swollen  areas  of  a  densely  elastic  consistence  cutting  like 
bacon,  mottled  reddish-yellow  or  grayish-yellow  and  leaving  on  the 
knife  blade  a  turbid  muco-purulcnt  juice.  In  tlie  chronic  type  the 
pulmonary  tissue  is  changed  into  an  extremely  tough,  light  grayish- 
yellow  mass  of  connective  tissue  riddled  with  confluent  cavities  about 
as  large  as  a  thumb's  breadth,  filled  with  a  slimy,  oily  pus  and  having 
a  deeply  reddened  inner  surface.     In  this  type  of  change  the  lymph 


%;\>^" 


Fig    79. 
Large  glanders  ulcer  of  nasal  septum  of  horse. 


glands  become  very  large  and  swollen,  soft  like  marrow ;  afterwards 
densely  indurated  and  changed  into  a  tough  white  connective  tissue, 
forming  nodular  bunches  as  large  as  a  goose  tgg  which  become  ad- 
herent to  the  surrounding  structures  by  similar  fibrous  bands.  In 
the  interior  of  these  hyperplastic  and  inflamed  lymph  glands  is 
encountered  either  a  purulent  softening  in  isolated  spots  or  exten- 
sive purulent  liquefaction  with  cavity  formation,  or  an  indurated, 
drv  cheesy  necrotic  focus.  The  multiplication  of  the  glanders 
bacilli  in  the  lymph  paths,  besides  causing  them  to  swell  up  like 
cords,  also  gives  rise  to  a  diiTuse  gelatinous  infiltration  (especially 
because  of  the  lymph  stagnation),  and,  if  the  inflammation  become 
chronic,  to  broad  connective  tissue  thickenings  ;  so  that,  for  example, 
the  loose  cellular  tissue  of  the  skin  becomes  the  seat  of  gelatinous 
thickening  with  extensive  indurations  all  through  it  (pachydermia, 
elephantiasis)  with  foci  of  suppurative  necrotic  destruction  running 
all  through  the  skin  and  subcutaneous  tissue. 


3i8  Specific  Inflammations. 

These  more  important  anatomical  changes  of  glanders  are  met 
associated  with  each  other  and  succeeding  one  another ;  so  that 
along  with  the  pneumonic  infiltration  of  the  pulmonary  lobules 
glanders  nodules  are  apt  to  be  met  in  the  same  case;  along  with 
the  abscesses,  ulcers  also  are  encountered,  the  latter  developing 
from  the  former,  and  the  diffuse  infiltrations  occurring  a§  a 
terminal  chang-e. 

Glanders  generally  may  be  considered  as  an  irrecoverable  infec- 
tious disease ;  exceptions  have  been  met  occasionally  in  man,  guinea- 
pigs  and  horses,  but  are  so  rare  that  attempts  to  cure  are  hardly 
worth  the  effort  in  the  case  of  animals,  and  seem  to  be  injudicious, 
when  the  daily  danger  is  considered  of  the  transmission  of  the  in- 
fection to  man  and  other  animals  from  the  subjects  dragging  out 
the  course  of  their  disease  for  months  and  years.  The  only  rational 
method  of  exterminating  tlie  disease  consists  in  killing  the  animals 
and  carefully  doing  away  with  every  chance  of  harm  from  any  ani- 
mal known  to  be  afflicted  with  glanders ;  and  these  provisions  should 
be  made  binding  by  law. 

For  details  concerning  the  aetiology,  symptoms  and  prophylaxis,  refer- 
ence may  be  made  to  Friedberger  and  Frohner,  Vcicrinary  Pathology, 
Amer.  Ed.,  W.  T.  Keener  &  Co.,  Chicago,  1904;  Xocard-Leclainche,  Lcs 
maladies  microbiennes  des  anitiiaux.     Ill  edition,   Paris,   1903. 

Actinomycosis. 

Actinomycosis  {SlktU,  ray;  tJ.vKr,s,  iungns) ,  or  Ray-fungus  Disease, 
is  a  form  of  wound  infection  manifesting  itself  bv  the  anatomical 
changes  of  a  suppurating  granulomatous  inflammation ;  it  may  be 
caused  by  several  varieties  of  a  group  of  fungi  known  as  the  rav 
fungi  or  actinomycetes.  It  occurs  not  infrequently  in  man,  cattle 
and  swine  and  has  been  exceptionally  observed  also  in  sheep,  hart 
and  roe  deer,  dogs,  cats  and  elephants. 

The  fungi  which  cause  the  affection  were  first  discovered  bv 
Langenbeck  in  1845  i"  the  carious  lumbar  vertebrae  of  a  man,  later 
by  Rivolta  in  1868  in  tumors  of  the  jaw  in  cattle  and  by  C.  Hahn 
in  1870  in  the  tongue  in  cattle  ;  and  have  been  more  fully  investigated 
by  Bollinger.  Harz,  Johne,  Israel,  Ponfick.  Gasperini,  Berestnew, 
Bostrom  and  others.  They  have  wide  distribution  in  nature,  existing 
especially  in  field  soil  and  the  beards  of  cereals.  The  usual  mode 
of  infection  b\"  the  ra}-  ftingi  is  through  wounds  made  by  small  for- 
eign bodies  penetrating  into  the  skin  or  inucous  membranes,  as  sharp 


Actinomycosis. 


319 


spicules  of  grain  or  other  stiff  particles  of  food  t(^  which  the  fungi 
are  adherent;  or  they  may  gain  access  to  the  tissues-  through 
scratches  and  similar  lesions  of  the  skin.  '  Examples  of  such  mode 
of  infection  are  common.  Persons  who  put  heads  of  grain  into  their 
mouths  or  who  accidentally  swallow  portions  of  such  heads  or  who 
have  been  injured  while  harvesting,  have  been  known  to  develop 
at  the  points  of  injury  (gums,  throat,  hands)  actinomycotic  ab- 
scesses and  growths.  Swine  pastured  in  stubble  land  where  their 
teats  are  casilv  wounded  by  the  stiff  straw  stubble  are  not  infre- 

Zu  nffen  b  csis 

©?*■ 

Rachenrvand 


Fig.    80. 

Fiiugous    actinomvonsis    in    pharynx    of    cow.      Actiiioin  iiciiiit .    actinomycotic    tumor. 
h'lUliciiinnul,  wall  of  pharynx.      Zuninnhnxix.   base  ot   tongue. 

quenth  known  to  develop  actinomycosis  of  a  mammary  gland. 
Cattle  frequently  show  actinomycosis  of  the  t®ngue,  gums  or  lips 
along  with  the  presence  in  the  tissues  oi  spicules  of  grain  or  other 
food  materials  which  have  been  forcibly  lodged  in  between  the  teeth, 
in  the  pharynx,  etc.  Occasionally  in  castration  the  fungi  from  the 
straw  of  the  bedding  get  into  the  operation  wound  and  set  up  acti- 
nomycosis of  the  stump  of  the  seminal  cord  and  scrotum  (for  de- 
tails cf.  Schlegel  and  Kitt*).  The  occurrence  of  actinomycosis  oc- 
casioned in  some  such  accidental  way   (pasturing  in  stubble  fields) 

*Hnnrn>.    der  pathoij.    Mikrnon/..    v.    Kolle    and    Wassermann :    Gustav    Fischer, 
Jena,    1003.     Kift    liactcncnktindr    fiir    Tierdrzte,    W     Autl.    W  len..    1JU4, 


320  specific  Inflammations. 

has  more  frequently  been  observed  than  an  actual  epidemic  affection 
(Bang,  C.  O.  Jensen,  Preusse). 

Transmission  of  actinomycosis  from  one  animal  to  another  or  to 
man  is  very  improbable ;  the  few  alleged  cases  of  such  an  occurrence 
which  have  been  recorded  in  literature  might  equally  well  have  been 
caused  by  traumatic  infection.  Artificial  transmission  by  inocula- 
tion has  been  successful  only  in  a  few  cases  (Johne,  Wolff  and  Is- 
rael, Ponfick  and  others),  and  in  these  the  experiment  animal  had 
to  receive  rather  deep  inoculation  with  comparatively  large  amounts 
of  the  infectious  material  (intraperitoneal,  subcutaneous  injection); 
while  in  ordinary  wound  infection  and  feeding  transmission  failed 
completely. 

The  anatomical  changes  brought  about  by  the  actinomycotic  in- 
fection include  the  formation  of  actinomycotic  nodules,  abscesses 
and  fungous  granulomatous  proliferations,  sometimes  accompanied 
by  indurative  connective  tissue  proliferations. 

The  actinomycotic  nodules  (actinomycosis  nodularis)  are  small 
inflammatory  foci  of  the  size  of  a  millet  seed  to  that  of  a  pea,  yellow- 
ish-red or  grayish-yellow  in  color,  composed  of  a  soft  granulation 
tissue,  which  is  developed  as  the  product  of  a  demarcating  inflam- 
mation about  the  fungus  which  acts  as  a  foreign  body.  They  show 
one  or  a  number  of  opaque  yellow  punctiform  spots  from  the  pres- 
ence in  minute  foci  within  them  of  the  yellow  colored  clumps  of 
fungi  and  pus  cells.  •  When  they  are  in  the  parenchyma  of  an  organ 

they  are   surrounded   by   a   connective   tissue 

^■^.-^^^^rr/flff'^  ^°"^  °^  induration ;  when  on  mucous  surfaces 

^M^^^W?^>P^MM.        t'ley  break  through  and  project  somewhat. 

^^■'^^M'^-'^^^F  ^cti^^omycotic     abscesses     (actinomycosis 

^'?^iii^^  pi^rulenta,  apostematosa)  are  areas  of  soften- 

mg  from  the  size  of  a  plum  stone  to  that  of  a 

'^'      ■ ,  human    head,    with    purulent    content    which 

Actinomj'cotic   clump. 

fAftci-  ostertag.)  either  appears  as  a  thin  mushy  fluid,  creamy 

and  of  a  sulphur  yellow  color,  enclosed  in  a 
white  indurated  abscess  wall,  or  the  areas  are  made  up  of  a  flabbv, 
grayish-yellow  to  reddish-yellow  matrix,  which  contains  the  infil- 
trating pus,  not  in  separate  foci  large  enough  to  allow  it  to  be  taken 
out  in  a  spoon,  but  just  as  though  it  were  in  a  fine  sponge.  In  the 
latter  case  there  is  no  real  abscess  membrane  present,  although  the 
surrounding  tissue  for  some  distance  is  converted  into  an  indurated, 
dense  white  connective  tissue. 

The  fungous  actinomycotic  grozvths  (actinomycosis  fungosa) 
look  like  mushrooms  or  soft  cushions,  projecting  above  the  surface 


Actinomxcosis. 


321 


of  the  skin  or  mucous  membrane.  They  are  more  or  less  peduncu- 
lated growths,  varying  in  size  from  that  of  a  nut  to  that  of  a  fist, 
covered  with  blood  and  pus  and  crusts,  with  an  elastic,  soft  consist- 
ence, on  section  looking  like  bacon,  grayish-white  or  grayish-red, 
and  thickly  beset  with  points  of  suppuration  or  the  described  flabby 
yellow  patches  of  softening. 


& 


^/.^•i 


i  A?': 


j'^^'i 


-% 


X* 


O  U^}:'' 


Fig.    82. 

\„dnlp   .,f   actinomvcosiy    (high   uiaguitteation )  :    </.    fibroblastic   and    epithcliuid    l)ui- 

der';    b,   leucocytic   central   pdrtion  :    c,   actmoniyces. 

All  three  of  these  forms  may  occur  together  and  pass  into  each 
other.  For  example,  after  rupture  of  an  abscess  the  granulomatous 
proliferation  springs  up  and  grows  out  as  a  fungous  mass;  or  the 
small  nodules,  because  of  the  progressive  multiplication  of  the  fungi, 
become  confluent  and  form  the  larger  flabby  areas  of  softening ;  or 
the  bacon-like  connective  tissue  growth  prevails,  and  this  causes 
more  or  less  marked  induration  of  the  organ. 

The  most  characteristic  thing  about  the  actinomycotic  growth  is 
the  fungus.  This  may  be  recognized  even  by  the  unaided  eye  as 
minute  granules  the  size  of  a  sand  grain,  soft  like  tallow  or  some- 
times of  a  chalky  consistence,  of  a  sulphur-yellow  color  or  white; 


322 


SpeciHc  IiiHamiiiotiojis. 


they  may  often  be  present  in  large  numbers  in  the  softened  areas 
and  the  pus  from  this  may  sometimes  have  an  ahnost  sand-Hke,  gritty 
consistence.     Under  the  microscope  the  fungi  may  be  discerned  in 


Fig.  83. 
Head   of   cow    with    actinomycosis    of   Jaw.       (After    Moiissu.) 

unstained  preparations  as  strongly  refractive,  gray  or  shining-yellow 
clumps  of  club-shaped  filaments  arranged  in  the  form  of  a  rosette 
(fungus   glands)  :   in   stained    sections   the   filamentous,    intricately 


Fig.  84. 
Actinomycosis  of  tbe   nasal  mucous   membi-ane  of  cow. 

branched  mycelium  forming  the  matrix  may  be  seen,  and  the 
clump,  with  its  budding  elements  swollen  into  club  shape  and 
growing    out    from    the    periphery    in    radiating    fashion.*      The 

*  For  fuller   description   cf.    Kitt,   Bakterienkunde   f.    Tierarste,  IV   Aufl.,    Wien. 
M.   Perles  Verl.     1903. 


Actiiioiitycosis.  323 

clumps  of  fungi  are  always  surrounded  by  leucocytes  in  the  fatty 
and  granular  detritus,  sometimes,  too,  with  here  and  there  a  giant 
cell.  About  this  central,  softened  focus  proliferating  fibroplastic 
tissue  is  formed,  vascular  and  full  of  emigrated  leucocytes,  as  a 
zone  of  varying  width. 

Actinomycosis  is  primarily  a  local  affection,  rutming  a  course  of 
months  or  years  in  duration.     As  the  fungi   penetrate  the  lymph 
spaces  and  are  carried  to  new  positions  fresh  eru])tions  in  multiple 
foci  of  infiammation  along  the  lymph  vessels  and  in  the  lymph  glands 
arise,   with   purulent   softening  and   coincident   production  of   new 
tissue   in  the   soft  parts  and   in   the  bones.      By  hgemic  convection 
also  the  process  may  become  a  general  one,  a  number  of  organs, 
bones,  etc.,  becoming  synchronously  or  one  after  another  involved. 
[In  cattle  one  of  the   most  common  and  characteristic   results  of 
actinomycotic   infection   is   that   seen  in   involvement    of    the    jaw, 
which  may  well  illustrate  many  of  the  features  of  the  disease.     The 
infection   here   is   supposed   to  take  place  by  the  penetration  of  a 
small    spicule    of   grass    or   beard    of    grain    into    the    gum    along 
the    root    of   the    tooth,    such    a    foreign    element    having    upon    it 
the  actinomycotic  fungus.     In  unknown  way  die  fungus  penetrates 
along  the  root  well  into  the  alveolar  process  of  the  jaw,  and  there 
produces  the  small  nodules  above  described,  each  undergoing  cen- 
tral softening  and  disintegration,  and  being  surrounded  by  a  zone 
of  new   tissue   formation   at   its  periphery.     Gradually  the  process 
loosens  the  teeth;  and  as  they  are  elevated  in  their  sockets  by  the 
inflammatory    tissue,    and    chewing   becomes    painful,    the    animal 
stops  eating.     Sometimes  the  teeth  are  forced  up  so  tliat  the  animal 
is  unable  to  close  the  mouth  without  pain,  and  the  teeth  may  even 
be  lost.      The   process   gradually   spreads   throughout   the   alveolar 
bone  and  into  and  through  the  whole  thickness  of  the  jaw,  the  in- 
flammatory  change  about   each   nodule  at  first  causing  absorbtion 
of  the  calcareous  matter,   and  thus  giving  the   fungi  a  chance  to 
spread  in  this   softened  tissue.     As   each  nodule  grows  older,  the 
formative  tissue  at  its  periphery  produces  new  bone :  and  from  the 
coincident   operation   of   the   two   factors  of  bone   destruction  and 
bone  formation  the  jaw  becomes  enormously  enlarged  ("big-jaw"), 
riddled  with  the  small  points  of  softening  representing  the  different 
actinomycotic  foci  and  with  fistulous  paths  running  all  through  the 
mass,  connecting  these  points  of  disintegration.    The  jaw  may  thus 
have  developed  wdthin  and  upon  it  a  tumor-like  mass  the  size  of  a 
double  fist  or  much   larger,   composed  of  a   coarse   framework  of 


324  specific  Inflammations. 

newly  formed  bone  like  a  coarse  calcareous  sponge,  tlie  meshes  of 
which  are  occupied  by  the  actinomycotic  nodules  and  their  purulent 
matter.  Fistulous  sinuses  discharge  upon  the  surface  and  into  the 
mouth ;  and  in  the  purulent  material  are  to  be  seen  the  tiny  yellow 
sand-like  grains  known  as  "sulphur  grains,"  consisting  of  the  fungi 
themselves.  The  animal  may  die  from  starvation ;  the  process  may 
extend  along  the  ramus  of  the  jaw  to  the  base  of  the  skull  and 
gradually  advance  by  the  same  changes  through  the  latter  and  cause 
death  from  a  purulent  meningitis ;  or  the  fungi  may  be  carried 
along  the  lymphatics  of  the  neck  to  the  thorax,  producing  an  acti- 
nomycotic pleurisy  and  entering  the  lung  to  cause  fibrosis  and  puru- 
lent destruction  of  these  organs.  Occasionally  the  fungi  swallowed 
with  tlie  discharge  into  the  mouth  give  rise  to  alimentary  actino- 
mycotic abscesses.] 

Lignieres  and  Spitz  have  described  an  epidemic  disease  of  cattle 
similar  to  actinomycosis  occurring  in  Argentina,  in  which  the  skin  and 
lymph  glands  are  principally  involved  (rarely  the  bones  of  the  face  and 
tongue).  The  yellow  fungus  grains  are  not  present,  and  another  species  of 
microphyte  which  does  not  stain  by  Gram's  method  is  regarded  as  the 
cause    {actiiiobacillosis). 

Botryomycosis. 

By  the  term  botryomycosis  is  meant  a  productive  inflamma- 
tion which  leads  to  the  formation  of  fibrous  growths  or  cicatri- 
cial indurations  attended  invariably  with  suppuration  and  fistula 
formation  or  the  production  of  brownish  to  yellowish-red  foci  of 
softening,  and  which  are  caused  by  infection  with  botryomyces 
ascoformans.  The  disease  is  quite  common  in  the  horse;  and 
has  been  met  a  very  few  times  also  in  the  cow  and  hog  (Csokor, 
Wilbrandt). 

The  fungus  which  is  the  productive  agent  of  the  disease,  dis- 
covered independently  by  Bollinger  in  1870,  Rivolta  and  Micel- 
lone  in  1879,  and  by  Rabe  and  Johne,  presents  itself  in  the  dis- 
eased tissue  as  a  deposit  of  fine  sand-like  granules,  visible  to  the 
naked  eye.  iMicroscopically  it  is  characterized  by  the  occurrence 
of  the  fungi  in  blackberry-like  masses  (fifty  to  one  hundred 
micromillimeters  in  size)  made  up  of  conglomerated  round,  disc- 
like masses  of  cocci  grouped  together  in  zoogloese.* 

This  fungus  gains  entrance  to  the  tissue  by  infection  of 
wounds ;   apparentl\-   it  may   find   its   way  through   small   excoria- 

*  For  fuller  description  cf.  Kltt,  Bakterienkunde  fiir  Tier'drzte.  IV  Aufl., 
Wien,  1903. 


Botryomxcosis  Tnnwrs. 


325 


tions  in  the  epiderni  nr  llin)nj;h  tlie  o-lands  of  the  skin,  as  botryo- 
mycotic  growths  develop  especially  at  places  in  the  skin  which 
are  frequently  subject  to  friction  (places  worn  by  harness  and 
saddle.)  Very  frequently  the  growth  involves  the  stump  of  the. 
spermatic  cord  after  castration,  or  the  udder  and  penis  sheath,  as 
well  as  the  bursas  and  fasciae  of.  the  withers,  elbow  and  shoul- 
der. The  tissue  invaded  by  these  microorganisms  becomes  the 
seat  of  a  chronic  inrtammation.  At  tirst  it  has  a  grayish-red  color, 
later  becoming  pale  and  translucent  (like 
bacon)  ;  and  eventually  a  white  cicatricial 
connective  tissue  develops  in  the  mass, 
spreading  through  the  loose  cellular  tissue 
and  over  the  surfaces  of  the  fasciae  and 
producing  enormous  induration  and  thick- 
ening* of  the  part.  Or  the  process  may 
be  more  definitely  limited  to  spheroidal 
nodular  masses  which  project  from  the  sur- 
face as  fibroma-like  tumors,  ranging  in  size 
from  that  of  a  fist  to  that  of  a  human  head 
or  larger.  The  growth  of  the  clumps  of 
microorganisms  in  this  fibroplastic  tissue  brings  about  foci  of 
softening  of  a  viscid  purulent  type,  sometimes  of  a  distinct  yel- 
low color  like  ordinary  pus,  but  commonly  of  a  safit'ron  or 
orange  tint,  with  formation  of  fistula?  to  the  surface  and  paths  of 
confluence  in  the  mass.  As  the  result  of  multiple  coincident  or 
successive  infection  of  the  skin  there  often  are  met  dozens  of  these 
botryomycomata  in  one  subject.  Convection  of  the  microbic  agents 
by  the  lymph  and  blood  leads  to  metastatic  growths,  especially  in 
the  lungs. 


Fig.    85. 

Botiyoinyces   ascofonnans 
(low  power). 


For    fuller   account    cf.    Kitt.    Sprcicllc   patliol. 
II.  Aufl.     F.  Enke,  Stuttgart,   1901. 


\natoinic    dcr    Ilaiiticri 


New  Growths,  Tumors,  Autoblastomata. 

By  the  terms  new  growths,  tumors,  new  formations,  neo- 
plasms, autoblastomata  (Klebs).  ore  meant  tissue  proliferations 
of  persistently  progressive  eliaracter,  li'hieh  alter  the  conforma- 
tion of  the  part  and  disturb  its  function.  These  growths  appear 
as  excessive  tissite  accumulations  caused  by  cells  of  the  animal 
body  which  have  become  parasitic  in  nature  and  Avhich  invade 
the  soft  structures  or  skeleton  of  the  animal  as  more  or  less 
isolated  and  independent  bodies.     Enlarging  sometimes  slowly, 


326  Tumors. 

sometimes  rapidly,  and  never  undergoing  diminution,  they  inter- 
fere with  the  other  tissues,  perhaps  by  robbing  them  of  their 
nutrition,  perhaps  by  some  of  the  products  of  their  metaboHc 
changes,  but  particularly  in  a  mechanical  way  by  their  pressure 
influences. 

It  has  been  only  within  the  last  sixty  years,  since  Rudolf 
Virchow  by  comprehensive  histological  studies  and  critical 
examination  of  the  older  literature  established  a  new  basis  for 
the  systematic  consideration  of  the  different  types  of  tumors, 
that  a  scientific  conception  of  the  origin  and  nature  of  new 
growths  has  entered  into  their  study  {oncology;  6  6yKos,  node). 
Previous  to  this  period  tumors  were  classified  mainly  from  their 
external  appearances  and  their  gross  anatomical  characteristics, 
and  were  named  frequently  from  incidental  features  often  of 
merely  accidental  prominence ;  and  no  real  knowdedge  was  had 
of  the  developmental  history  of  these  growths.  Although  in 
our  present  knowledge  of  the  development  of  tumors  there  are 
many  missing  links,  we  nevertheless  possess  from  microscopic 
and  experimental  investigations  sufficient  information  in  regard 
to  their  nature  to  permit  us  to  clearly  recognize*  their  derivation 
from  the  cells  of  the  body,  the  mode  of  their  extension  and  their 
actual  method  of  growth,  and  the  significance  of  the  pathological 
process  in  its  bearing  upon  the  life  of  the  subject. 

Tumors  may  te  classified  from  their  histogenesis,  that  is, 
from  their  structure  and  from  their  origin  and  construction  from 
the  cells  and  tissues  of  the  body.  There  are  no  foreign  tumor  ele- 
ments brought  into  the  body  from  without ;  tumors  are  offsprings 
of  the  body  cells,  and  are  accordingly  found  to  consist  of  these 
and  of  the  intercellular  substances  of  the  various  tis-;ues.  They 
develop  according  to  the  same  laws  which  govern  the  embryonic 
development  and  later  growth  of  the  individual  and  the  processes 
of  regeneration  ;  and  they  arise  from  the  four  primary  types  of 
body  tissue  (connective  tissue  in  all  its  forms,  epithelium,  muscle 
and  nervous  tissue.) 

Just  as  the  tumor  cells  present  the  same  form  and  the  same 
mode  of  multiplication  as  the  mother  cells  from  which  they  are 
derived,  the  intercellular  substances,  as  products  of  the  cells,  are 
the  same  as  are  produced  by  the  original  cells.  Generally,  there- 
fore, the  source  of  a  tumor  can  be  determined  from  the  character 
of  its  tissue ;  although  because  of  the  fact  that  they  grow^  more 
or  less  independently,  as  isolated  masses  of  tissue,  it  is  quite 
reasonable  to  expect  more  or  less  modifications  in  the  structure 


Classification   of  Tmnors.  327 

and  adaptation  of  the  cells  and  matrix  of  tumors.  The  cells 
frequently  do  not  attain  the  same  size  as  the  mother  cells  or 
may  be  larger  than  the  latter ;  cellular  division  takes  place  some- 
times as  a  direct  process,  sometimes  indirectly  with  mitotic 
changes.  The  mitotic  figures,  which  are  likely  to  be  found  in 
great  numbers,  especially  in  rapidly  growing  tumors,  and  the 
process  of  cellular  division  often  show  irregularities  pointing  to 
a  pathological  disturbance  of  the  process.  The  chromatin  fila- 
ments derived  from  the  chromatin  skein  (chromatosomes)  may 
be  too  numerous  or  asNinmetrical ;  or  there  may  be  found  giant 
mitoses,  karyokinetic  figures  in  multipolar  arrangement,  arranged 
about  a  number  of  attraction  centres  (centrosomes),  or  giant 
cells.  The  cells  may  also,  as  stated  by  Ribbert,  exhibit  altera- 
tions which  may  be  regarded  as  regressive  in  character,  as  a 
return  to  an  embryonic  state  in  which  there  is  but  little  evidence  of 
differentiation ;  or  they  may  really  be  embryonic  cells  whose 
power  of  forming  normally  functionating  organs  has  been  lost 
(a  change  designated  by  Hansemann  by  the  term  Anaplasia) . 

The  cellular  type  and  the  character  of  the  tissue  of  the  growth 
furnish  the  basis  for  nomenclature  of  tumors.  Many  tumors  are 
made  up  of  but  a  single  kind  of  tissue,  as  fibrous  connective 
tissue,  fat  tissue  or  cartilage,  or  at  least  mainly  of  one  type  (the 
accompanying  bloodvessels  are  not  regarded  as  a  special  form  of 
tissue  but  as  essential  constituents  of  any  form)  ;  such  growths 
are  called  simple  autohlastomata.  Others,  no  less  numerous, 
contain  two  or  more  tissues,  as  is  obviously  required  in  epithelial 
new  growths  because  epithelium  always  requires  a  connective 
tissue  substructure,  and  as  is  likely  to  occur,  too,  in  other  tumors 
from  the  mixture  of  the  various  forms  of  connective  tissue,  as 
cartilage,  bone  or  fat ;  we  therefore  recognize  as  a  second  group, 
the  compound  autohlastomata  or  mixed  tumors. 

It  should  be  recognized,  too,  that  tumors  as  independent  devel- 
opments, although  relying  on  the  animal  body  for  their  nutri- 
tion, yet  having  their  own  blood  vessels  and  carrying  on  a 
separate  metabolism,  are  subject  to  all  the  pathological  processes 
which  may  affect  the  normal  tissues  of  the  body.  A  tumor  may 
become  the  seat  of  passive  hyperaemia,  of  inflammatory  reaction ; 
and  any  kind  of  degeneration  and  necrosis  may  occur  in  the 
tumor  structure.  Tumors  are  sometimes  subject  to  traumatic 
influences  from  without  (strangulation,  wrenching,  penetration 
by  foreign  bodies  or  bacteria)  which  may  occasion  tissue 
changes;  sometimes  the  conditions  of  nutrition  become  so  un- 


328  Tumors. 

favorable  from  irregularities  of  g'rowth  of  the  individual  con- 
stituents of  the  tumor  (as  the  imperfect  development  of  blood 
vessels)  or  from  the  absence  of  ducts  for  the  escape  of  secre- 
tions, or  from  the  retention  of  metabolic  products,  that  regres- 
sive metamorphoses,  as  fatty  degeneration,  calcification,  mucoid 
degeneration,  etc.,  necessarily  take  place.  When  such  condi- 
tions prevail  and  when  the  structure  of  the  growth  is  modified  by 
this  or  that  change  there  is  often  considerable  difficulty  in  deter- 
mining the  derivation  of  the  tumor  and  there  may  be  much  un- 
certainty under  which  group  of  tumors  a  given  neoplasm  should 
be  classed.  In  such  cases  we  follow  the  proverb :  a  potiori  fiat 
deiiominafio ;  and  the  anatomical  term  is  given  from  the  pre- 
dominating type  of  tissue  present. 

Growth  of  Tumors. — Derived  from  one  or  more  tissues,  tumors 
at  first  form  cellular  masses  (or  a  tissue  complex).  These  in- 
crease in  size  as  the  internal  portions  of  the  new  formation 
multiply,  that  is,  by  centra!  growth;  or  they  enlarge  by  progres- 
sive multiplication  of  the  outer  portions,  that  is,  by  peripheral 
or  appositional  growth.  The  increase  in  size  and  extension  of 
the  tumor  therefore  may  take  place  by  one  or  other  of  two  ways ; 
either  by  the  tumor  growing  "as  a  bulb,  lying  in  the  soil  and 
developing,  presses  aside  the  ground"  (Diirk).  "as  a  rubber  bal- 
loon which  one  inflates''  (Ribbert)  (expansile  growth),  or  by 
the  tumor  tissue  sending  out  processes  into  the  neighboring  struc- 
tures as  a  plant  forces  its  roots  into  the  earth  (infiltration  growth). 
It  was  formerly  believed  that  the  enlargement  took  place  by  the 
surrounding  tissues  becoming  gradually  involved  in  the  same 
proliferative  process,  being  actually  infected  (local  infection)  ;  but 
this  is  not  probable,  as  we  may  usually  recognize  under  the  micro- 
scope that  the  proliferating  cells  of  the  :neoplastic  primary  focus, 
that  is,  the  first  elements  of  the  tumor,  are  extending  into  the 
surrounding  tissue,  growing  mto  the  interior  of  the  tissue  or 
toward  the  surface  of  the  part.  The  surrounding  tissue  supplies 
only  the  nutrition  for  growth  and  takes  part  only  in  this  sense 
that  its  blood  vessels  and  supporting  tissue  may  be  appropriated 
by  the  new  growth,  and  that  it  may  also  multiply  as  the  result 
of  the  changes  in  tissue  tension  which  may  be  produced  (v. 
chapter  on  Regeneration)  ;  otherwise,  however,  the  surrounding 
tissue  plays  but  a  passive  part,  like  the  soil  in  relation  to  the 
seed  of  grain. 

External  Shape  of  Tumors. — In  correspondence  with  their 
mode    of    growth    autoblastomata     form     usually      circinnscribed 


Tumor  Shapes;  Sii^nificance  of   Tumors.  329 

tumors  well  tlefined  from  the  normal  tissues.  They  may  develop 
as  nodes  (tuherous  growths)  which  lie  embedded  in  the  tissue 
like  the  yolk  within  an  egg,  or  niay  protrude  as  tuberosities;  they 
may  grow  out  from  the  surface  of  an  organ  as  pedunculated 
protuberances,  with  thick  pedicle  like  a  mushroom  (fungous  form), 
or  with  slender  pedicle  and  provided  with  free  offshoots  like  a 
polyp  with  its  tentacles  (polypous  shape),  or  like  a  tree  (den- 
tritic), like  a  coral  stalk  or  like  cauliflower;  or,  in  the  infiltrating 
varieties  they  may  occasion  a  uniform  szcelling  of  the  affected 
organ.  [Anv  tumor  growing  from  a  surface  and  provided  with  a 
slender  pedicle  may  be  spoken  of  as  a  polyp  or  a  polypoid 
groii'th,  whether  branched  or  smooth.  A  form  known  as  a  flat 
tabular  s-u'elling  is  often  encountered  where  upon  a  surface  the 
growth  has  produced  a  more  or  less  uniform  swelling  with  a 
flattened  surface,  as  is  often  seen  where  the  surface  of  a  growth 
is  opposed  by  a  second  surface  causing  pressure.  The  causes 
determining  the  various  shapes  of  tumors  include  such  factors  as 
the  mode  of  growth  (central  growth  producing  a  regular  ap- 
pearance of  the  periphery,  while  infiltrative  growths  are  apt  to 
be  irregular  and  ragged  in  outline),  pressure,  (as  just  suggested 
in  connection  with  the  flat  tabular  swelling,  or  the  preservation  of 
the  spheroidal  shape  of  v  node  by  the  pressure  from  all  sides  by 
the  surrounding  tissues,  or  where  an  analogous  growth  appears 
as  a  tuberosity  or  polyp  if  developing  close  to  a  surface,  being  thus 
relieved  of  pressure  on  the  surface  side),  and  the  original  structure 
from  which  the  tumor  arises  (as  where  a  surface  growth,  a 
papilloma,  takes  on  ■  a  villous  type  of  branching  following  the 
natural    formation    of    villi    from    the    original    tissue,    as    in    the 

intestine.)] 

The  Pathological  Significance  of  Tumors  is  determined  pri- 
marilv  bv  their  location,  their  size  and  the  mechanical  pressure 
which  the}'  exert  upon  the  adjacent  tissues.  By  pressure  upon 
the  peripheral  tissues  a  tumor  as  it  grows  in  size  occasions  some- 
times trifling  and  at  other  times  serious  disturbance  of  func- 
tion, varying  with  the  particular  organ  affected.  A  small 
tumor  in  the  brain  or  in  the  cranial  cavity  may  by  compression 
of  the  fonuer  or  of  the  cerebral  vessels  bring  about  most  intense 
nervous  troubles  and  terminate  fatally;  and  by  obstructing  the 
larynx,  gullet  or  intestinal  canal  a  comparatively  small  growth  may 
endanger  life.  Pressure  upon  bloodvessels  may  occasion  a  great 
variety  of  circulatory  disturbances.     But,  on  the  other  hand,  even 


330  Tumors. 

large  growths   of  the   skin   or   subcutaneous  tissue   often   produce 
only  the  most  trifling  effects. 

In  the  second  place  the  pathological  significance  depends 
upon  the  degree  of  special  power  which  the  tumor  possesses  to 
disseminate  through  the  system.  The  less  a  tumor  involves 
strictly  the  surface  of  an  organ  or  the  less  it  remains  closely 
confined  to  its  point  of  origin  as  a  single  isolated  growth,  and 
the  more  it  sends  out  oilshoots  which  extend  into  the  lymph- 
passages  and  bloodvessels  and  thus  obtains  opportunity  for  its 
cells  to  be  loosened  and  carried  into  new  locations  in  the  body, 
the  more  the  development  of  the  neoplasm  acquires  specially 
dangerous  characteristics.  The  outshoots  of  a  tumor,  made  up  of 
its  proliferating  cells,  force  their  way  first  in  the  surrounding  tis- 
sue, especially  the  connective  tissue  lymph  spaces,  which  repre- 
sent the  beginnings  of  tlie  lymph  passages,  causing  a  continually 
increasing  portion  of  the  organ  in  which  the  growth  occurs  to  be 
destroyed  by  the  infiltration  (the  tumor  therefore  spoken  of  as  a 
destructive  growth  or  locally  penetrating  grozcth).  In  such  new 
formations  the  external,  visible  outlines  are  usually  not  its  actual 
limits;  the  apparently  healthy  adjacent  tissue  may  conceal  the 
roots  of  the  tumor  only  to  be  found  microscopically.  The  sur- 
geon, whose  skill  can  in  many  cases  aft'ord  permanent  recovery 
by  removal  of  the  growth,  is  unable  occasionally  (for  technical 
reasons  or  because  the  precise  limits  of  tht  individual  roots 
cannot  be  recognized  by  the  unaided  eye)  to  remove  the  entire 
tumor  in  the  operation  performed  for  its  ablation ;  from  the 
portions  thus  left,  earlier  or  later  the  same  tumor  may  return  in 
the  original  site  or  close  by  (recurrence  of  tuuior).  The  tumor 
cells  grow  into  the-  lymph  passages,  sometimes  as  continuous 
cords  or  roots ;  or  the  cells  may  become  loosened  or  be  carried 
away  by  the  lymph  current  or  perhaps  by  leucocytes.  The 
same  thing  occurs  where  the  roots  of  the  tumor  penetrate  through 
the  wall  of  a  blood  vessel,  sometimes  developing  as  long  pro- 
cesses within  its  lumen ;  and  particles  of  the  growth  may  be 
swept  off  by  the  blood  current.  Under  such  circumstances,  at  a 
shorter  or  longer  distance  from  the  (primary)  autoblastoma  (the 
principal  tumor)  arise  secondary  tiiinors.  daughter  tumors  or 
metastatic  tumors.  The  lymphogenous  metastases  are  carried 
into  the  immediately  adjacent  tissues  and  into  the  lymphatic 
glands  draining  the  site  of  the  original  growth;  the  embolic 
(haematogenous)  ones  pass  into  the  lungs  or  the  organs  of 
the  greater  circulation  (v.  chapter  on  Embolism).    When  in  this 


Pathological  Si^^nUicancc  of  Tumors.  331 

manner  the  tunuir  is  disseminated  widely  to  the  various  organs, 
we  speak  of  the  generalisation  of  the  tumor.  This  lodgment  and 
development  of  daughter  nodules  from  the  cells  which  have  be- 
come freed  from  a  tumor,  an  actual  form  of  seeding  by  trans- 
plantation, is  met  also  at  contact  points  on  mucous  and  serous 
surfaces.  For  example,  an  ovarian  tumor  may  become  dissem- 
inated all  over  the  peritoneum  by  having  its  cells  loosened  and 
scattered  over  the  serous  membrane ;  a  tumor  of  the  costal  pleura 
may  become  transplanted  to  the  visceral  pleura ;  one  of  the 
upper  lip  to  the  lower  lip.  The  cellular  elements  of  the  growth 
in  such  instances  are  freed  and  distributed  by  the  movements  of 
the  viscera,  or  by  the  friction  of  contiguous  surfaces. 

All  secondary  growths  correspond  closely  with  the  primary 
tumor  from  which  they  arose  in  their  histological  structure; 
where  a  cancer  of  the  gum  metastasizes  to  the  retropharyngeal 
lymph  glands  and  lungs  the  metastatic  formations  are  composed 
of  squamous  epithelial  cells  just  as  is  the  primary  tumor.  They 
need  not  necessarily  be  smaller  than  the  original  giowth,  and 
are  often  of  larger  size  than  the  latter. 

Tumors  which  can  be  completely  removed,  which  are  not  metastatic 
and  do  not  recur,  are  ordinarily  called,  from  the  clinical  point  of  view, 
benign  (innocent)  ;  those  which  penetrate  into  the  adjacent  tissues  and  are 
removed  in  their  entirety  with  difficulty,  or  are  recurrent  and  give  rise 
to  metastases,  are  called  malignant  (harmful).  To  the  extent  that  experi- 
ence shows  that  one  or  othe--  of  these  results  may  generally  be  expected 
in  operations  for  removal,  the  classification  into  these  two  types  may  be 
accepted;  but  the  differences  are  not  to  be  depended  upon,  as  some  tumors 
which  do  not  form  metastases  recur  if  not  completely  removed,  and 
tumors  which  are  ordinarily  regarded  as  benign  may  occasionally  produce 
metastases;  and,  again,  well-known  malignant  growths  often  remain  strictly 
localized  and  harmless  for  a  long  time,  and  if  they  are  removed  early 
enough  will  not  recur. 

As  a  further  factor  by  which  tumors  may  affect  the  system, 
it  should  be  recalled  that  within  these  neoplasms  all  sorts  of 
metabolic  products  and  decomposition  substances  are  being  freed, 
and  these  may  by  absorption  have  toxic  influences  upon  the 
possessor  of  the  growth.  It  is  quite  common  to  meet  with  in- 
flammatory changes  in  the  tissue  about  a  tumor  and  the  growth 
itself  may  be  found  richly  infiltrated  with  immigrating  leucocytes, 
or  rnay  be  found  undergoing  suppurative  or  gangrenous  changes. 
This  may  be  due  to  the  fact  that  tumors  which  happen  to  be  situated 
on  exposed  surfaces  are  invaded  by  bacteria,  and  the  toxines 
of  the  latter  excite  inflammation  ;  but  there  is  little  doubt  that 


332  Tumors. 

some  tumors  give  off  into  the  surrounding  tissues  metabolic  pro- 
ducts having  chemotactic  power  and  thus  stimulate  leucocytes 
to  escape  from  the  vessels.  To  all  appearances  we  may  ascribe 
to  the  products  of  disintegration  Occasioned  by  bacterial  contam- 
inations and  occurring  in  connection  with  the  various  degenera- 
tions in  tumors  the  fact  that  in  a  number  of  these  growths 
there  occur  general  nutritive  disturbances  (oligsemia,  loss  of 
appetite,  marked  loss  of  strength,  emaciation),  which  look  like 
the  result  of  a  chronic  intoxication — a  condition  known  as  tumor 
cachexia. 

Just  as  the  specifically  differentiated  cells  of  the  body  give 
off  specific  products,  in  the  same  way  the  different  kinds  of 
tumor  cells,  as  the  offspring  of  this  or  that  variety  of  physio- 
logical cells,  produce  in  more  or  less  similar  manner  the  sub- 
stances characteristic  of  the  latter ;  it  may  be  claimed  that  they 
too  perform  physiological  functions.*  This  function,  however, 
is  only  in  the  rarest  instances  of  any  service  to  the  general 
system ;  being  without  au}^  relation  to  the  co-ordinated  activities 
of  the  rest  of  the  organs,  it  is  merely  a  vital  phenomenon  of 
the  independent  cellular  complex  of  the  tumor.  The  formation 
of  intercellular  substances  by  the  tumor  cells,  as  the  formation 
of  osteoid  callus  in  tumors  arising  from  periosteum,  is  an 
example  of  such  function ;  but  tumors  originating  from  gland- 
ular cells  and  having  gland-like  structure  show  this  power 
especially,  and  are  able  to  produce  the  sam'e  secretory  sub- 
stances as  the  corresponding  glands.  Thus  cancers  of  the  intes- 
tinal mucous  membrane  secrete  mucus  from  goblet  cells;  thyroid 
cancers  produce  colloid ;  tumors  of  the  mammary  gland  form  a 
secretion  analogous  to  milk  (but  pathologically  altered),  and 
tumors  arising  from  liver  cells  often  secrete  so  much  bile  that 
the  growth  becomes  thoroughly  infiltrated  with  it  (icteric).  E. 
Albrecht  has  observed  that  the  formation  of  red  blood  corpuscles 
normally  performed  by  the  bone  marrow  may  also  be  carried 
on  by  a  tumor  of  the  dura  mater  made  up  of  endothelial  cells 
and  erythroblasts. 

As  all  offsprings  of  given  cells  manifest  an  ability  given  them 
by  heredity  to  perform  the  same  fimctions  as  their  predecessors, 
it  may  be  expected  that  the  metastatic  nodules  also  show  the 
same  phenomenon.  For  example,  one  of  a  number  of  metastatic 
nodes  which  had  formed  in  the  lung  from  a  tumor  originating  in 

*E.  Albrecht,  Sitsungshericlit  d.  morph.  pln/s.  Gesellschaft  in  Miinchen, 
1901.    Heft  II. 


Causes  of  Tumors.  333 

the  liver  produced  bile  in  tliis  position,  (lenerall}-  the  secretions 
of  tumors  are  apt  to  be  the  seat  of  pathological  changes,  as  ordi- 
narily there  are  no  channels  for  discharge  in  the  growth  and  the 
secretion  therefore  is  stagnant;  and  moreover  the  function  would 
be  more  or  less  abnormal,  because  of  the  abnormal  topographical 
relations  of  the  proliferated  glandular  epithelium,  the  failure  of 
complete  differentiation  of  the  cells,  or  the  reversion  of  tumor 
cells  to  embryonic  type  and  the  lack  of  relation  with  the  nervous 
system  of  the  host  of  the  tumor. 

There  are  conditions  however  under  which  the  secretory  pro- 
ducts of  a  tumor  are  not  devoid  of  value  to  the  body,  particu- 
larly tumors  of  glands  which  produce  internal  secretions  of  im- 
portance to  metabolism  and  whose  destruction  would  be  ominous 
to  the  well-being  of  the  body,  as  the  thyroid  gland  and  pancreas. 
The  fact  that  growths  from  these  glands  may  also  produce 
internal  secretions  may  in  some  measure  compensate  for  the 
death  or  destruction  of  the  organ  by  the  tumor. 

[Of  all  the  body  functions,  that  of  growth  (and  that  is  rather 
a  mere  vital  phenomenon  and  not  a  dift'erentiated  function)  is  the 
one  which  is  best  and  most  completely  manifested,  being  in  line 
with  the  embryonic  characteristics  which  tumors  as  a  class 
possess.  The  example  of  the  performance  of  a  function  of  value 
to  the  economy  selected  by  the  author  in  the  preceding  para- 
graph is  practically  the  only  one  which  may  be  named.  The 
fat  which  accumulates  in  a  lipoma  is  of  no  service  to  the  host 
of  the  tumor  even  if  he  be  starving;  the  connective  tissue  of  a 
fibroma  is  of  no  connective  or  supportive  value,  but  rather  a 
continual  source  of  annoyance  from  weight  and  pressure.  Even 
the  function  of  growth,  most  nearly  typifying  natural  energy,  is, 
as  the  author  points  out.  irregular  in  the  manner  of  its  occurrence, 
is  without  efficient  organogenic  power  and  especially  abnormal  in 
that  it  has  no  definite  period  of  cessation.] 

Aetiology  of  Tumors. — We  possess  but  few  facts  and  have  but 
a  meagre  idea  about  the  mode  of  origin  of  tumors.  Many  the- 
ories have  been  framed  to  explain  the  luxuriant  growth  of  the 
cells,  but  the  diffiiculty  of  positive  proof  leaves  us  in  uncer- 
tainty between  probabilities  and  theoretical  dicta.  Mere  supposi- 
tions that  as  the  result  of  the  action  of  a  given  stimulus  this  kind 
or  that  kind  of  cells  are  excited  into  irrepressible  multiplication, 
revert  to  their  embryonic  characteristics  or  undergo  biological 
changes  as  expressed  by  the  terms  metaplasia  or  anaplasia, 
are  in  no  sense  satisfying,  but  merely  serve  to  conceal  our  igno- 


334  Tumors. 

ranee  of  the  origin  of  these  growths  and  to  bring  into  the  prob- 
lem new  difficulties. 

Among  the  more  prominently  urged  hypotheses  may  be  men- 
tioned the  idea  that  an  infections  cause  underlies  the  cellular 
proliferation,  a  view  which  has  had  numerous  adherents  in  re- 
cent years.  At  first  bacteria  were  sought  as  causative  factors, 
some  of  which  as  the  causes  of  productive  inflammation  had  mani- 
fested functions  suggesting  analogies  with  tumor  formation ; 
but  nothing  has  been  shown  beyond  the  mere  secondary  presence  in 
tumors  of  various  saprophytes,  pyogenic  and  other  bacteria ;  and 
no  microphytes  have  been  encountered  which  can  be  regarded 
as  responsible  for  the  proliferation  of  cells  into  tumors.  In  time 
the  line  of  investigation  was  directed  to  the  protozoa.  The  in- 
clusions, often  shown  by  a  variety  of  methods  of  staining  in  many 
tumor  cells,  and  apparently  of  foreign  character  (that  is,  intracellu- 
lar and  nuclear  structures  not  conforming  to  normal  parts  of  cells), 
led  a  number  of  microscopists  to  regard  them  as  of  some  type 
of  protozoan  character  and  as  the  parasitic  causes  of  cancer  and 
malignant  tumors  generally.  However  subsequent  investigations 
directed  to  the  final  proof  of  this  discovery  have  shown  that  these 
supposedly  foreign  elements  are  nothing  more  than  altered  blood 
corpuscles,  lymphocytes,  nuclei  of  the  tumor  cells,  degeneration 
products  or  artefacts,  produced  by  stains  and  reagents  in  the 
tissues.  In  the  same  way  the  discovery  of  yeast  fungi  having 
pathogenic  properties  capable  of  causing  inflammatory  granu- 
lomatous formations  by  inoculations  in  small  experiment  ani- 
mals, resulted  in  no  definite  or  generally  applicable  conclusions ; 
because  these  blastomycetes  were  not  to  be  found  in  true  tumors. 
or  if  occasionally  found  occurred  only  on  the  surface  of  the 
growth  and  failed  to  give  rise  to  characteristic  tumors.  With 
the  demonstration  of  parasites  as  causative  agents  left  in  this  unsat- 
isfactory condition,  consideration  should  be  given  to  the  so-called 
invisible  microorganisms ;  or  we  should  remember  that  perhaps 
with  our  present  technique  the  infectious  agents  in  question 
cannot  be  rendered  visible. 

A  number  of  investigators  insist  upon  the  possibility  that  an 
infectious  factor  underlies  some  types  of  tumors  (Sticker), 
because  as  a  matter  of  fact  there  have  been  noted  a  number  of 
peculiar  circumstances  which  point  to  the  existence  of  a  general 
extraneous  (not  individual)  cause;  as  the  endemic  occurrence  of 
cancer,  its  occurrence  in  connection  with  dermal  excoriations,  or 


Causes  of  Tumors.  335 

the  occurrence  of  dermal  proliferatimis   ( pai)ill(iinata  )   in  a  number 
of  horses  in  the  same  stable. 

However,  a  great  number  of  objections  have  been  raised  against 
the  parasitic  hypothesis,  especially  by  Ribbert,  which  leave  this 
method  of  causation  in  extreme  doubt.  In  the  first  place  the 
various  forms  of  tumors  always  have  their  fixed  tissue-charac- 
teristics, and  the  cells  of  the  metastatic  nodules ,  invariably  con- 
form with  th(^se  of  the  original  growth  ;  if  an  infection  were  the 
cause  of  the  tumors  it  would  always  have  to  cause  the  production 
of  the  same  kind  of  cells  in  the  various  organs  (that  is,  the  cause 
of  a  cylindrical  cell  cancer  in  the  intestine  would  have  to  be 
able  to  form  cylindrical  intestinal  epithelium  in  the  interior  of 
the  liver;  the  cause  of  a  squamous  epithelioma  would  have  to 
form  keratous  flat  epithelial  cells  in  the  lymph  glands).  How 
that  could  occur  cannot  be  understood;  it  would  have  to  be 
assumed  that  the  cells  were  so  intimately  associated  with  the 
parasites  that  both  should  always  go  together  and  grow  together. 
If  such  symbiosis  be  claimed  to  actually  exist,  then,,  as  Ribbert 
logically  argues,  it  must  be  assumed  that  the  microorganism 
invariably  divides  at  the  same  time  as  the  tumor  cells  so  that 
one  of  its  offspring  may  be  present  in  each  of  the  two  new 
cells.  "If  this  be  not  essential,  it  may  be  asked  how  the  cells 
which  do  not  contain  parasites  come  to  proliferate  any  further. 
If  they  are  able  to  multiply,  however,  without  the  existence 
of  their  parasites,  why  was  it  of  essential  importance  that 
the  latter  should  have  ever  been  present?"  (Ribbert).  Then 
there  is  the  established  fact  that  every  tumor  grows  from  its  own 
substance  under  direct  pressure  contact  from  the  contiguous 
parts,  and  the  surrounding  tissue  does  not  become  infected;  there- 
fore the  parasite  would  have  to  confine  its  multiplication  strictly 
within  the  tumor  cells.  This  would  be  strange ;  and  the  question 
naturally  arises,  why,  for  example,  the  neighboring-  epithelia 
which  are  quite  like  those  of  a  skin  cancer  do  not  furnish  equally 
favorable  soil  for  the  development  of  the  microorganisms.  In 
the  end,  as  Ribbert  emphasizes,  we  should  have  to  assume 
that  for  every  new  growth,  for  every  type  of  cell  of  malignant 
tumors,  there  exists  a  special  type  of  infectious  agent  incapable 
of  infecting  otlier  cells,  as  one  special  form  for  cylindrical  cell 
cancers,  another,  for  squamous  cell  cancers,  etc.  The  genesis  of 
tumors  would  become  progressively  more  and  more  complicated 
if  such  ideas  w^ere  to  prevail. 


336  Tumors. 

The  explanatory  theories  of  Cohnheim  and  Ribbert  based 
upon  considerations  of  embryology  and  mechanical  conditions  for 
growth  are  far  more  simple.  Tumors  have  been  repeatedly  met 
in  the  new  born ;  for  example  a  melano-sarcoma  in  a  calf,  a 
papilloma  in  a  foal,  and  a  number  of  growths,  which  although 
first  noted  in  young  animals  were  of  a  composition  necessitating 
an  embryonal  origin  for  their  development,  as  dermoid  cysts, 
dental  teratomata,  branchial  cleft  teratomata.  In  the  earliest 
stages  of  embryonic  development  w^hen  in  a  great  variety  of  ways 
there  occur  formation  of  folds  and  of  buds,  pressure  displace- 
ments and  separations  of  the  cells  growing  with  unequal  rapidity, 
it  is  possible  that  cells  and  groups  of  cells  may  be  cut  off  from 
the  rest,  misplaced  or  isolated.  Such  misplaced  cells  will  for 
the  most  part  perish,  because  of  the  necessarily  occurring  nutri- 
tive disturbances ;  but  where  according  to  circumstances  the 
nutrition  remains  sufficient  the  misplaced  cells  will  continue  to 
grow  and  multiply,  and  there  is  necessaril\'  produced  from  them 
a  structure  which  is  apparently  a  foreign  growth  and  not  nor- 
mally belonging  to  the  structure  of  the  tissues  and  organs.  The 
formation  of  blood  vessels  probably  proceeds  in  a  more  or  less 
atypical  manner  in  such  separated  and  misplaced  groups  of  cells. 
as  a  result  of  which  their  growth  is  in  one  instance  a  very  slow 
one,  in  another  an  exuberant  cellular  proliferation.  The  experi- 
mental studies  of  Roux  have  shown  that  by  artificial  isolation 
and  misplacement  of  segmentation  cells  each  one  is  capable  of 
growing  into  an  embryo;  and  Barfurth  has  observed  that  after 
needling  an  ^gg  in  the  gastrula  stage  tumor-like  formations 
(dern^oid-like)  develop  from  the  misplaced  cells.  J^Ioreover  Rib- 
bert has  succeeded,  by  transplantation  of  fragments  of  the  auricle 
of  a  rabbit,  in  obtaining  polypoid  nodules  persisting  for  more 
than  a  year,  consisting  of  skin,  fibrous  tissue,-  cartilage  and 
bone ;  and  in  other  experiments  tumor-like  structures  from  bits 
of  the  notochord,  by  transplantation  to  the  anterior  surface  of  the 
intervertebral  tissues.  Occasionally  the  accidental  or  intentional 
operative  transplantation  of  epithelium  or  bits  of  skin  into  a 
wound  has  resulted  in  the  formation  of  a  small  epithelial  cyst  or 
dermoid  cyst  from  the  engrafted  tissue,  which  may  be  regarded 
as  evidence  in  the  same  line  with  the  larger  congenital  growths 
of  this  type.  The  fact  that  experiments  of  this  sort  have  thus  far 
failed  to  produce  larger  tumors  of  progressiva  and  persistent 
character  of  growth  is  not  an  argument  against  this  theory ;  we 
must  remember,  as  Ribbert  insists,  that  our  technique  in  artificial 


Causes  of  Tumors.  337 

isolation  and  transplantation  of  tissues  is  as  yet  not  delicate 
enough  to  prevent  damaging  the  tissues  and  thus  causing  the 
failure  of  the  desired  results. 

Cohnheim  extended  his  theory  of  the  embryonic  origin  of 
timiors  to  a  wider  application  by  advancing  the  hypothesis  that 
at  an  early  period  of  embryonal  developinent  more  cells  may  be 
formed  than  are  needed  in  the  construction  of  the  organs  and 
that  some  of  these  cells  may  remain  unused  as  "rests,"  retaining, 
because  of  their  embryonal  nature,  a  marked  capacity  for  prolif- 
eration;  and  that  from  such  excesses  of  cellular  material  tumors 
may  develop.  The  views  advanced  by  Cohnheim,  to  whom  we 
are  indebted  for  first  pointing  out  the  important  significance  of 
foetal  isolation  of  cells  in  connection  with  tumor  formation,  are 
coming  to  be  recognized  as  valid ;  that  from  isolated  segmenta- 
tion cells,  which  have  actually  been  observed,  tissues  and  organs 
may  originate,  and  in  all  probability,  too,  independent  tissue 
formations  and  therefore  autoblastomata. 

In  a  somewhat  different  form  practically  the  same  hypothesis  has  been 
recently  advanced  by  J.  Beard.  Beard  suggests  that  from  every  fertilized 
ovum  a  number  of  germ  cells  originate  (?),  from  which,  however,  only 
one  goes  to  form  the  embryo,  the  remaining  wandering  into  the  embryonic 
mass  and  entering  into  the  formation  of  the  chorion  (or  the  sexual  cells?). 
It  may  be  possible  that  a  tumor  might  develop  from  such  wandering  germ 
cell  if  it  stray  to  an  improper  part,  and  that  such  a  tumor  may  be  abso- 
lutely nothing  but  an  incompletely  developed  (rudimentary)  embryo  (which, 
of  course,  is  applicable  for  a  number  of  tumors,  especially  the  true 
teratomata). 

As  a  further  application  of  Cohnheim's  theory,  which  it  is 
true  afifords  a  satisfactory  explanation,  not  for  all  but  for  a 
number  of  tumors,  Ribbert  has  suggested  that  cells  may  escape 
from  their  normal  connection  also  in  extra-uterine  life  and  thus 
become  misplaced  and  in  consequence  provide  the  nucleus  for  a  tu- 
mor formation.  It  has  been  repeatedly  noticed  that  tumors  have 
developed  after  a  traumatic  lesion,  at  the  site  of  injury  by  foreign 
bodies,  after  contusion,  etc.,  as  osteomata  of  the  jaw  after  contu- 
sion, large  chondromata  in  animals  and  man  after  fracture  of  the 
ribs  at  the  seat  of  the  fracture,  cancer  of  the  cheek  in  man  after 
being  hit  by  a  stone,  cancer  of  the  lip  at  the  place  where  the 
mouthpiece  of  a  tobacco  pipe  has  been  frequently  rubbing.  As 
it  is  ver}'  difficult  to  think  of  such  cases  being  due  to  any  specific 
irritative  influence  of  the  foreign  body  which  caused  the  injury, 
we  are  forced  to  consider  changes  in  the  positions  of  the  cells, 


338  Tumors. 

displacements  and  isolations  of  osteoblasts,  cartilage  tissue  or 
epithelium,  as  causative  of  the  autoblastomatous  new  formations. 
It  is  not  rare  to  see  connective  tissue  proliferations  of  considerable 
extent,  completely  reproducing  the  characteristics  of  fibromata, 
developing  from  injuries  of  the  tendon  sheaths  (horse  and  cow) 
or  of  the  tongue  (cow)  ;  the  growth  is  apparently  the  product  of 
a  chronic  inflammatory^  process  and  the  result  of  an  excessive 
growth  of  granulation  tissue.  \Miether  some  special  irritant, 
perhaps  bacteria,  bring  about  such  tumor-like  formations, 
whether  absence  of  tissue  tension  occasioned  by  the  trauma  is 
the  single  or  principal  reason  for  its  occurrence,  remains  an 
open  question.  At  all  events  it  is  recognized  that  there  are  no 
sharp  lines  of  difference  between  tumors  and  regenerative  prolif- 
erations, and  that  the  hypertrophies,  which  are  regarded  as  sim- 
ple proliferations  in  vacuo  (as  of  liver)  may  pass  over  into 
tumors. 

Objections  have  been  urged  from  various  sides  (Hansemann, 
Hanau,  Ziegler)  to  the  opinions  of  Ribbert  (who  also  accepts 
inflammatory  processes  as  possible  causes  for  the  inception  of  cel- 
lular proliferations,  as  in  case  of  epithelial  cells).  It  has  been 
urged  that  if  the  above-mentioned  displacements  and  isolations 
of  cells  of  epithelium  were  sufficient  to  call  a  cancer  into  exis- 
tence, there  necessarily  should  develop  numberless  cancers  as 
results  of  chronic  inflammatory  phlegmons  ;  that  the  cells  of  the 
tumors  ought  not  to  appear  merely  as  normal  elements  in  luxuri- 
ant multiplication,  but  the  general  rule  should  be  that  there  exist 
a  special  change,  a  differentiation  of  the  cells  (even  though  the 
causes  of  cellular  dift'erentiation  be  entirely  unknown). 

Although  we  still  await  the  solution  of  questions  regarding 
the  conditions  which  underlie  the  origin  of  tumors,  and  concerning 
the  transformation  of  this  or  that  kind  of  cell  into  tumor  cells, 
it  is  at  least  certain  that  tumor  cells  are  tissue  elements  zvhich 
hare  become  independent  and  m(iy  be  looked  upon  as  cells  zvhich 
have  actually  become  parasitic.  This  conception  of  the  nature  of 
tumors  (for  which  from  this  point  of  view  the  name  autoblasto- 
mata,  proposed  by  Klebs,  is  most  appropriate)  has  received  im- 
portant support  in  the  extremely  interesting  experimental  studies 
of  a  veterinarian,  C.  O.  Jensen.  This  investigator  succeeded  in 
carrying  a  carcinomatous  tumor  of  a  mouse  through  nineteen 
generations  in  mice  by  transplantation,  and  in  demonstrating  that 
infection  played  no  part  in  the  process  but  that  the  transplanted 
tumor  cells,  themselves  parasitic  upon  the  individuals  in  whom 


Causes  of  Tumors.  339 

they  were  transplanted,  continued  to  grow  and  form  tumors  of 
the  size  of  walnuts,  growths  of  considerable  size  wdien  that  of 
the  experimental  animal  is  taken  into  consideration.*  Earlier 
than  this  Hanau  had  succeeded  in  transferring  an  unquestionable 
skin  cancer  of  one  rat  to  other  rats  wath  similar  results  (in  peri- 
toneal cavity)  ;  and  L.  Loeb  and  Velich  have  successfully  trans- 
planted rat  sarcomas,  and  Aloran  has  transplanted  adenocarcin- 
omata  of  a  white  mouse  a  number  of  times.  [Still  more  recently 
L.  Loeb  has  carried  an  adenocarcinomatous  tumor  of  a  Japanese 
dancing  mouse  through  a  number  of  generations,  eventually  find- 
ing a  change  in  the  nature  of  the  tumor  which  took  on  the  histo- 
logical characteristics  of  a  spindle  cell  sarcoma.  Other  investi- 
gators have  described  similar  success  in  transplantation ;  and 
Loeb's  instance  of  change  in  the  tumor  characteristics  is  not  an 
isolated  one.]  (Attempts  to  transplant  sarcomas  and  can- 
cers in  dogs  undertaken  as  much  as  ten  years  ago  by  Piitz  and 
other  investigators  have  thus  far  failed.)  The  point  of  special 
interest  in  Jensen's  studies  is  the  discovery  that  it  is  possible, 
by  special  methods  of  implanting  the  tumor  cells,  to  render  the 
diseased  mice  immune  so  that  the  tumors,  which  are  present  in 
them  and  which  are  ordinarilv  fatal,  disappear  and  the  subjects 
recover.  Jensen  brought  about  this  result  in  two  ways,  first  by 
treating  the  diseased  mouse  wath  its  own  tumor  cells,  substances 
developing  in  consequence  in  the  blood  (cytotoxins),  which  in- 
hibited further  extension  of  the  tumor  cells  at  the  original  site 
(v.  Chapter  on  Immunity)  :  and  second  by  repeated  introduction 
of  the  tumor  cells  into  rabbits  (not  susceptible  to  the  mouse 
carcinoma)  he  obtained  a  serum  wdiich  manifested  specific  cyto- 
toxic action.  [In  a  similar  set  of  transplanted  adenocarcinomata 
of  mice  Gaylord  found  that  some  of  the  affected  individuals  re- 
covered naturally,  their  tumors  after  more  or  less  growth  under- 
going atrophy  and  disappearing.  From  such  individuals  he  ob- 
tained a  serum  which,  when  introduced  into  mice  with  marked 
tumor  growths,  uniformly  caused  their  disappearance  by  its 
cytolytic  power.] 

The  tissue  of  tumors  isolated  from  the  body  will  retain  its  vitality  at 
a  temperature  of  from  i°-3°  C.  for  about  eighteen  days,  at  room  tempera- 
ture for  about  twelve  days,  but  at  body  temperature  for  scarcely  twenty- 
four  hours.  This  difference  is  supposed  to  be  due  to  the  cells  passing 
into  a  sort  of  resting  condition  at  the  lower  temperatures,  while  at  the 
body   temperature    they    cannot    avoid    metabolism. 

♦For  details  v.  Centralbl.  f.  Bakteriol.  u.  Par-asitenkiaulc,  1903,  No.  1,  ;>^XX!V 
Pd. 


340  Tumors. 

Statistics  of  Tumors  in  Animals;  Influence  of  Age  and  Sex.— It  has  only 
been  within  very  recent  times  that  any  attempt  has  been  undertaken  to 
systematically  collect  the  material  relating  to-  the  frequence  of  tumor  occur- 
rence in  animals  (Johne,  Frohner,  Casper,  Sticker).  It  is  very  difficult 
at  the  present  time  to  draw  any  comparison  of  these  data  with  those 
of  man  whose  tumor  involvements  have  for  many  years  been  subjects 
of  careful,  conscientious  and  extensive  statistics  in  literature.  The  early 
slaughtering  of  the  food  animals  is  partly  at  fault,  as  many  tumors  are 
not  apt  to  appear  until  advancing  age.  This  is  especially  true  of  cancer, 
according  to  Frohner;  which  in  dogs  is  not  encountered  at  all  for  the  first 
two  years,  and  is  met  with  any  degree  of  frequency  only  in  old  dogs; 
eighty-seven  per  cent,  of  his  animals  affected  with  cancers  were  over  five 
years  of  age,  fifty-four  per  cent,  over  seven  years  old  (in  man  cancer  is 
most  frequent  between  the  fortieth  and  seventieth  year — about  seventy  per 
cent.).  While  in  man  cancer  is  of  special  frequence  on  the  lips,  stomach 
and  uterus,  in  these  sites  the  tumors  are  very  rare  in  animals  (gastric 
cancer  has  been  observed  but  one  time  in  the  dog— Eberlein).  Sarcomata, 
however,  are  mainly  met  in  young  animals. 

As  far  as  sex  may  have  influence  upon  tumor  formation,  it  can  merely 
be  said  that  the  female  sexual  apparatus  in  animals  is  far  less  frequently 
involved  by  malignant  tumors  than  in  mankind;  only  in  the  mammary 
glands  of  bitches  are  various  tumors  to  be  met  with  any  frequence,  while 
cancers  of  the  genital  tract  occur  only  as  great  rarities. 

As  indicative  of  an  influence  exerted  by  the  species  upon  the  devel- 
opment of  tumors,  it  may  be  stated  that  cancer  is  relatively  frequent  in 
dogs,  melanosarcoma  and  cancer  in  horses,  and  sarcomas  in  cattle  and 
swine    (Casper). 

Resume  of  Tumors. — The  nomenclature  and  classification  of 
tumors  is,  as  explained  on  p.  326,  mainly  dependent  upon  their  his- 
togenesis, origin  and  tissue  composition.  The  existence  of  many 
types  of  component  tissues,  together  with  the  fact  that  cells  of  mul- 
tiplying tissue  may  present  all  sorts  of  shapes,  and  that  sometimes 
unusual  tissues  take  part  in  the  formation  and  that  it  is  often  im- 
possible to  determine  from  what  normal  type  of  tissue  the  tumor 
had  its  origin,  make  it  difficult  to  carry  out  the  classification 
strictly  upon  this  basis.  A  certain  number  of  tumors  present 
themselves  always  in  the  same  forms  and  these  can  be  sharply 
defined;  but  there  are  others  which  are  of  mixed  structure  and 
of  intermediate  types. 

The  principal  types  of  tumors  may  be  distinguished  as  fol- 
lows : 

I — Fibroma^  simple  fibrous  connective  tissue  tumor  or  fibrous 
tumor. 

2 — Lipoma^  fatty  tumor. 

3 — Myxoma,  mucoid  tumor. 


Fibroma.  341 

4 — Chondroma,  cartilaginous  tumor. 
5 — Osteoma,  bone  tumor, 
6 — Myoma,  niuscular  tumor. 
7 — Neuroma  and  Glioma,  nerve  tumors. 
8 — Hemangioma,  Lymphangioma,  vascular  tumors. 
9 — Sarcoma,  atypical  connective  tissue  tumor. 
10 — Lymphoma,  lymph  g'land  tumor. 
II — Melanoma,  pigmented  tumor. 
1 2 — Endothelioma,  Perithelioma,  Cholesteatoma. 
13 — Papilloma. 

14 — Adenoma,  epithelial  glandular  tumor. 
15 — Carcinoma,  atypical   epithelial  cancer  growth. 
16 — Epithelial  cysts,  Dermoids  (skin  tumors),  Odontoma,  Com- 
pound Teratomata. 

The  Lidii'idual  Types  of  Tumors. 

Fibromata. 

A  fibroma,  or  fibrous  connective  tissue  tumor,  is  a  growth 
made  up  of  adult  fibrous  connective  tissue,  that  is,  of  connective 
tissue  cells,  fibrils  and  bloodvessels. 

Fibromata  vary  in  consistence  with  the  degree  of  predom- 
inance of  their  fibrillar  basic  substance,  with  the  density  or 
looseness  of  the  bundles  in  which  the  fil:)res  are  united  and  the 
relative  presence  of  blood  vessels  and  lymph  vessels.  From  this 
point  of  view  two  types  of  these  tumors  are  distinguished,  the 
hard  and  the  soft  fibroma. 

The  hard  fibroma  (fibroma  durum)  is  met  as  rounded  nodes 
of  very  dense  consistence,  usually  presenting  the  firmness  and 
appearance  of  tendon  tissue,  cutting  with  a  tough  resistance  and 
creaking  on  section.  The  cut  surface  which  shows  but  little 
moisture  and  is  nearly  dry,  is  of  a  white  or  light  yellow  color, 
with  intermingled  shining  and  dead  w'hite  markings  from  the 
intricately  interwoven  bundles  of  fibres  (depending  on  whether 
these  are  cut  in  longitudinal  or  transverse  planes  of  section),  and 
with  a  fibrous  appearance.  The  tumor  as  it  expands  in  growth 
is  usually  sharply  defined,  presses  upon  the  adjacent  structures 
and  has  no  tendency  to  penetrate  them  ;  the  surrounding  tissue, 
however,  being  thinned  more  and  more  as  the  layer  over  the 
growth  is  stretched.  The  stretching  and  loss  of  tissue  tension 
may  cause  coincident  proliferation  of  these  adjacent  structures,  as 
epithelium,   over   the   tumor.      Under  the   microscope  the   bundles 


342  Tumors. 

of  fibres,  compactly  arranged  and  thick,  may  be  seen  running  in 
a  wavy  course,  usually  arranged  concentrically  about  the  blood- 
vessels and  often  of  considerable  length.  Between  the  fibres  are 
spindle  cells  with  spindle  shaped  nuclei,  and  occasionally  elastic 
fibres  are  intermingled. 

Sometimes  the  fibroma  develops  as  a  dift'use  growth,  giving 
rise  to  large  wooden-like  thickenings  of  the  subcutaneous  tissue, 
with  radiating  extensions  running  into  the  surrounding  struc- 
tures. 


v'^A    ; 


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^l^c 


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s 


'^.     '  ,^cV»' 


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f 


Fig.  86. 
Hard   fibroma  :    subcutaneous   nodule,   from   horse. 

The  soft  fibroma  (fibroma  moUe)  is  characterized  by  its  softer 
consistence,  and  the  greater  proportion  of  bloodvessels  and  lym- 
phatics in  its  construction.^  It  is  in  consequence  of  a  more  reddish- 
gray  color,  is  sometimes  gelatinous ;  and  its  shape  is  sometimes 
nodular  or  lobulated,  sometimes  with  a  villous  papillary  surface. 
Under  the  microscope  it  contains  in  addition  to  the  loosely  ar- 
ranged bundles  of  fibres  numerous  spindle  and  rounded  connec- 
tive tissue  cells  and  wandering  corpuscles,  and  is  quite  rich  in 


Fibroma. 


343 


blood  vessels.  The  soft  character  o'f  the  growth  is  due  partly  to 
the  numerous  cells  it  contains,  partly  to  the  presence  of  lymph 
fluid,  especially  where  the  latter  is  practically  stagnant  because 
of  twisting-  of  the  pedicle  of  a  pedunculated  tumor.  In  such  cases 
the   bundles   of   fibres   and   cellular   groups   are   separated   from 


Fig.  87. 
Fibroma    (myxomatous)    of   the   end   of  cow's   tail. 


344 


Tumors. 


each  other  and  meshes  are  formed  and  become  more  or  less  dis- 
tended, and  the  cells  take  on  branched,  stellate  shapes.  Such 
a  growth  is  also  known  as  fibroma  myxoiiiatodes  or  Hbromyxoma 
from  the  gelatinous  change  present  in  it ;  the  more  vascular 
reddish  ones  as  raspberry  polyps,  fibroma  angiomatodcs,  caver- 
iiosum   or  tclcangiectaticum. 

Occasionally  calcification  or  even  ossification  takes  place  in 


Fig.  88. 
Section   of  a   flbroma   from   a   liorse. 

the  tissue  of  fibromata,  producing  dull  white  foci  of  bony  hard- 
ness  (fibroma  pctrificans,  ossificans). 

Sometimes  the  fibrous  tissue  formation  is  found  about  the 
bloodvessels  or  about  the  glandular  ducts  or  nerves,  arranged  in 
circular  concentric  whorls  and  systems  of  bundles  about  these 
structures ;  such  growths  being  described  under  the  terms  plcxi- 
form  or  pericanalicular  fibromata. 

Fibromata  growing  from  scars  or  imperfectly  cicatrized  granulation 
tissue  from  wounds  are  apt  to  become  especially  dense,  consisting  of  thick, 
closel}'    packed,    interwoven    bundles    of    fine    fibrils,    are    known    in    human 


Fibroma.  345 

medicine  as  keloids  (x^^V,  the  claws  of  a  crab),  because  of  the  resemblance 
of  the  rounded  or  finger-like  nodes  to  the  legs  of  a  crab ;  in  man  spon- 
taneous keloids  arc  encountered  as  tumor  formations,  apparently  hereditary 
in  families. 

The  fibromatous  tisstte  may  combine  with  fat  tissue,  bone  or 
muscle  giving  rise  to  fibroUpomata,  fibro-ostcomata  or  fibromy- 
omata,  or,  when  the  second  type  of  tissue  predominates,  to  lipo- 
Hbromata,  ostcofibroinata  or  niyofibromata.  [It  is  not  a  matter 
of  special  importance,  but  generally  the  name  of  the  tissue 
predominating  is  given  as  the  basic  name  of  the  combined  tumor, 
contrary  to  the  above  statement.  Thus  wdiere  in  a  tumor  com- 
posed of  fibres  and  adipose  tissue  the  former  predominates  the 
growth  is  known  usually  as  a  lipofibroma :  where  the  latter  is 
the  more  important  constituent,  the  term  fibrolipoma  is  used.] 
In  case  of  an  associated  proliferation  of  the  epithelium 
covering  a  fibroma,  or  of  glandular  tissue  the  resultant  com- 
binations are  known  as  Hbropapillomata  and  Hbroadcnomata. 
Soft  fibromata,  more  particularly  because  of  active  proliferation 
of  their  cells  and  from  the  fact  that  these  young  cells  are  not  apt 
to  maintain  uniformity  of  shape  but  assume  in  varying  measure 
embryonal  characteristics  in  size  and  shape,  occasionally  acquire 
features  which  may  justify  the  name  fibrosarcoma. 

Fibromata  are  of  slow  growth,  usually  single  tumors,  but 
sometimes  primarily  multiple,  ranging  in  size  from  that  of  a 
nut  to  that  of  a  human  head  or  even  larger,  being  known  to 
weigh  as  much  as  one  hundred,  and  even  one  hundred  and  sev- 
enty-eight kilograms  (Wehenkel,  Siedamgrotzky).  Because  of 
the  wide  distribution  of  fibrous  connective  tissue  structures 
their  development  may  take  place  in  practically  any  part  of  the 
body,  although  there  are  certain  parts  in  which  they  appear  with 
especial  frequence.  The  places  of  election  are  the  skin  and 
subcutaneous  tissue,  especially  of  the  front  of  the  breast  (horse), 
the  dewlap  (cow),  the  elbows  (dog),  and  the  end  of  the  tail 
(cow).  In  these  situations  they  form  hard  nodular  swellings 
or  nodes  covered  with  epidermis,  or  in  other  instances  lobulated 
pedunculated  growths  {fibroma  pcndulans).  As  multiple  pri- 
mary formations  Siedamgrotzky  once  counted  in  a  thirteen-year- 
old  stallion  more  than  a  hundred  fibromata  in  the  skin,  which  had 
grown  in  the  course  of  three  months  in  the  breast,  abdomen, 
neck  and  face,  to  sizes  varying"  from  that  of  a  hazel  nut  to  that  of 
the  palm  of  the  hand.  Similar  multiplicity,  warranting  the  term 
fibromatosis,   has   been  observed   in   dogs  by  Frohner  and   Cadiot 


346  '  Tumors. 

(cited  by  Casper).  Fibromata  are  frequently  found  in  the  tongue 
of  the  cow,  as  well  as  in  the  vagina,  in  the  latter  situation  as 
pedunculated  growths  of  large  size  projecting  into  the  vaginal 
canal.  Those  fibromata  which  are  found  in  horses  and  cattle 
after  injury  of  the  skin  and  tendon  sheaths  at  the  joints  of  the 
feet  may  form  enormous  masses ;  they  are  apt  to  have  the  sur- 
faces covered  with  granulation  tissue.  Fibromyxomata  are  es- 
pecially common  at  the  end  of  the  tail  and  in  the  heart  (epicar- 
dium  and  endocardium)  as  pedunculated  growths,  as  well  as  in 
the  naso-pharnyx  (where  they  are  found  hanging  from  the  wall 
covered  with  mucous  membrane  and  are  known  as  nasal  polyps). 
The  author  has  observed  a  perfect  string  of  hard  rounded  fibro- 
mata in  the  lung  of  a  horse  (for  details  v.  Kitt,  Lelirhnch  d. 
spezicUcu  pathol.  Anatomic  d.  Haiisticrc,  Verl.  v.  Enke,  Stutt- 
gart, II.  Aufl.,  1901). 

A  fibroma  may  sometimes  be  harmful  because  of  its  size  and 
location  (occlusion  of  passages,  pressure  upon  vital  organs),  but 
does  not  give  rise  to  metastasis  and  usually  does  not  recur  after 
extirpation. 

The  hard  fibromata  of  the  skin  ami  tongue  undoubtedly  are 
often  results  of  traumatic  lesions.  The  connective  tissue  scle- 
roses resulting  from  injuries  by  foreign  bodies,  or  that  arising 
after  healing  of  an  actinomycotic  area,  a  chronic  botryomycosis 
or  even  a  malignant  oedematous  infection,  may  be  sometimes 
such  hard,  definitely  outlined,  biscuit-shaped  or  nodular  deposits 
and  prominences  that  an  anatomical  distinction  between  these 
sequels  of  chronic  productive  inflammation  and  true  tumors  can- 
not be  made. 

Lipomata. 

The  lipoma  or  fatty  tumor  is  made  up  of  adipose  tissue,  of 
clusters  of  fat  cells  in  various  stages  of  development,  along 
with  bloodvessels  and  fibrous  connective  tissue.  The  fat  cells 
are  apt  to  be  larger  than  those  of  normal  adipose  tissue.  These 
tumors  arise  from  situations  normally  rich  in  adipose  tissue,  as 
the  mesentery  or  subserous  peritoneal  fat.  where  they  frequentl}' 
occur  in  the  horse.  The  peritoneal  adipose  tissue  often  forms 
lobular  appendages,  which  when  much  overgrown  and  stretched 
by  the  intestinal  movements  become  pedunculated  and  present 
themselves  as  pearshaped  masses  or  tumors  of  the  size  of  a  fist. 
They  may  give  rise  to  fatal  intestinal  entanglements.     In  case 


Lipoma. 


347 


..^C^^^ 


<r^  V  /- 


--4»_ 


Fig.   89. 
Lipoma. 


Fig.  90. 


Loop  of  intestine  of  horse  strangulated  from  ilie  entanglement  of  a  lipoma. 


348  Tumors. 

of  rupture  of  the  pedicle  such  lipomata  become  loose  in  the 
peritoneal  cavity  and  may  be  found  at  autopsy  as  compressed 
free  bodies.  These  peritoneal  lipomata  present  a  smooth  surface, 
are  semitransparent,  yellowish  or  white.  Lobulated  lipomata  are 
found  also  in  the  cow  and  hog  in  the  omentum,  and  in  the  intes- 
tine and  perirenal  fat;  in  these  animals  the  fat  is  firm  and  white. 
The  subcutaneous  tissue  is  a  frequent  site  in  the  horse,  especially 
in  the  neighborhood  of  the  knees  where  tliey  may  attain  very  large 
size  (twenty-six  and  a  half  kilograms  in  a  case  reported  by 
Moller)  ;  and  in  the  dog  especially  on  the  inner  surface  of  the  thigh, 
in  the  fold  of  the  knee  (Frohner),  and  in  the  breast  (Stockfleth). 
As  submucous  growths  they  have  been  found  in  the  uterus  (a  lipo- 
ma of  a  cow  recorded  by  Lund  reaching  a  weight  of  seventy-five 
kilograms),  and  in  the  membrana  nictitans  in  the  horse  and  dog 
(Frohner).  Here,  too,  their  shape  is  nodular  or  lobular  and  the 
growth  is  usually  well  circumscribed  and  therefore  easily  shelled 
out. 

Sometimes  lipomata  appear  in  positions  where  adipose  tissue 
does  not  normally  exist;  thus  two  lipomata  of  the  size  of  a 
child's  head  have  been  found  in  a  dog's  liver  by  Trasbot,  small 
lipomata  in  the  kidneys  of  the  same  animal  (Bruckmiiller),  and 
Kuhnau  encountered  a  rare  instance  of  a  lipoma  of  the  brain  in  a 
three-year-old  beef  (four  centimeters  in  diameter,  rounded  and 
arising  from  one  of  the  bloodvessels  of  the  pia  mater).  This 
last  instance  was  congenital.  According  to  Bostrom  it  is  pos- 
sible that  a  bit  of  germinal  fat  tissue  of  the  skin  of  the  embryo 
might  have  been  separated  and  been  misplaced  in  the  cranial 
area.  Lubarsch  suggests  that  intraparenchymatous  renal  lipo- 
mata take  their  origin  from  portions  of  the  renal  capsule. 

Lipomata  occur  as  either  single  or  multiple  primary  growths. 
They  may  occasionally  undergo  mucoid  degeneration  (lipoma 
myxomatodes),  calcification  {lipoma  pctrificans)  or  dry  anaemic 
necrosis.  When  the  combined  fibrous  connective  tissue  is  espe- 
cially abundant  they  may  be  very  firm  (lipofibroma).  They 
are  slow  in  growth,  but  as  above  stated  may  attain  considerable 
size.  Those  which  are  situated  subcutaneously  may  be  easily 
extirpated ;  they  are  not  recurrent  and  do  not  give  rise  to 
metastases. 


Tumors.  349 

Myxomata. 

A  myxoma,  a  mucous  connective  tissue  tumor,  is  a  neoplasm 
which  consists  either  entirely  or  in  part  of  gelatinous  embryonic 
connective  tissue ;  and  therefore  its  tissue  closely  simulates  the 
Wharton's  jelly  of  the  umbilical  cord  in  consistence,  transparency 
and  texture.  It  is  characterized  microscopically  by  an  intercel- 
lular substance  rich  in  mucin,  in  which  are  sparsely  scattered 
cells  of  spindle   and   highly  branched  stellate   forms  with  long 


^ 


•^^ 


^:j 


\ 


hi 


^% 


S. 


Fig.  91. 
Myxoma. 

slender  prolongations;  while  here  and  there  are  to  be  seen  blood 
vessels  and  a  small  amount  of  fil^rillar  connective  tissue.  In 
fresh  material  the  mucinous  substance  may  be  precipitated  by 
the  addition  of  acetic  acid.  Often  only  individual  portions  of 
the  tumor  are  conspicuously  myxomatous,  the  remainder  being 
made  up  of  fat  tissue  or  dense  fibrous  tissue  (myxolipoma,  myxo- 
Hhroma)  ;  and  many  luxuriantly  growing  types  show  features 
of  transition  to  sarcoma  and  mixed  tumors  (myxosarcomata^. 
Occasionally     fibromata     and     lipomata     of     pedunculated     shape. 


350 


Chondroma. 


which  have  become  oedematous  from  lymphstasis,  simulate 
myxomata  (fibroma  myxomatodes),  the  absence  of  mucin  or  its 
scanty  proportion  in  the  fluid  content  distinguishing  them  from 
the  true  myxoma. 

Myxomata  develop  as  single  or  more  or  less  multiple  primary 
growths  according  to  their  situation,  and  as  sarcomatous  mixed 

tumors  capable  of  metastasis  and  of 
embryonic  appearance.  They  are  es- 
pecially met  upon  and  in  the  heart 
of  cattle  (when  the  subperi cardial 
and  subendocardial  foetal  mucous  tis- 
sue acts  as  their  developmental  sub- 
stance) as  rounded,  lobulated  growths 
ranging  in  size  from  that  of  a  nut  to 
tliat  of  a  fist ;  they  also  occur  in  the 
nose  in  the  cow  and  horse,  in  the 
parotid,  and  in  one  case  in  the  dog 
around  the  spinal  cord  (Holzmann). 
and,  too,  in  cattle  along  the  nerve 
trunks  (neuromyxoma).  The  gela- 
tinous, glassy,  swollen,  yellowish 
(sometimes  like  flesh  of  the  cod- 
fish) appearance,  their  softness  and  the  ropy  mucoid  character  of 
their  substance,  constitute  their  important  distinguishing  features. 


Fig.    02. 

Myxofibroma    of    the    heart,    from 
cow. 


Chondromata. 

A  chondroma  or  cartilaginous  tumor  has,  in  addition  to  a 
vascular  fibrous  connective  tissue  framework,  as  its  main  con- 
stituent cartilaginous  tissue,  usually  of  the  hyaline  type,  and 
contains  cartilaginous  cells  of  very  irregular  size  encapsulated  in 
this  substance  without  regularity  of  arrangement.  The  fibrous 
tissue  forms  a  capsule  and  the  trabecular  framework  about  the  dif- 
ferent cartilaginous  areas  (which  occur  as  islands  and  lobulated 
nodules  in  the  tumor)    and  acts  as  their  nutritive  perichondrium. 

Besides  the  pure  chondromata  there  are  met  manv  mixed 
types,  made  up  of  fibrous  tissue,  bone  and  glandular  tissue,  in 
which  cartilage  enters  as  only  one  of  the  constituents ;  and  modifi- 
cations may  also  result  from  the  rather  marked  tendencv  of  the 
cartilage  to  metamorphosis,  both  regressive  and  progressive.  Mu- 
coid degeneration  with  production  of  gelatinous  softened  foci 
(cysts),    and    calcification,    giving    rise    to    white    opaque    patches 


Chondroma. 


351 


(chondroma  cysticum,  myxomatodes,  petrificans)  are  especially 
likely  to  be  observed;  and  sometimes  ossification  (chondroma 
ossificans)  takes  place. 


.^"^ 


r 


X 


^ 


l-Hf 


A 


V 


Fig.  93. 
Chondroflbroma    of  ovary   of   sheep    (the   uterus    to   the   left). 

Chondromata  are  nodular,  nodose,  lobulated.  rounded  tumors 
of  dense  (in  case  of  myxomatous  change  or  when  other  tissues 
are  combined  they  are  softer)  consistence;  showing  their  car- 
tilaginous substance  as  a  milk-white,  grayish  and  bluish  w^hite, 
semitransparent  material.  They  may  attain  considerable  dimen- 
sions, perhaps  the  size  of  a  human  head,  and  may  weigh  from 
ten  to  twenty-eight  kilograms.  According  to  their  location  the 
cartilaginous  tumors  may  arise  from  previously  existing  cartilage 
(ecchondromata) .  or  may  develop  within  the  bone  marrow  or  in 
the  soft  tissues  which  do  not  contain  cartilage  (enchondromafa). 
The  former  originate  from  the  perichondrium,  the  cells  of  which 
are  usually  concerned  in  formation  of  cartilage  ;  the  latter  arise 
probablv    from    misplaced    embryonic    cartilaginous    rudiments. 


352  Tumors. 

Isolations  of  bits  of  tissue  from  either  of  these  sources  may  occur 
in  embryonic  Hfe  from  developmental  faults,  as  in  the  formation 
of  the  branchial  arches  or  the  primitive  vertebrae  and  embryonal 
elements  of  the  ribs.  The  fact  that  chondromata  may  be  congen- 
ital is  an  argument  for  this  view.  In  the  postfcetal  period  car- 
tilaginous isolations  may  take  place  from  disturbance  in  growth 
in  the  skeleton  (rachitis)  ;  and  traumatic  lesions,  as  fractures  of 
ribs,  may  give  origin  to  separation  of  bits  of  perichondrium,  and 


Fig.  94. 
•  Section   of   a   chondroma   from    a   hen. 

these  in  association  with  profuse  callus  formation  might  develop 
into  chondromatous  tumors. 

Chondromata  are  most  common  in  the  bony  framework  of  the 
chest  as  the  result  of  fractures  of  the  ribs,  projecting  into  the 
chest  cavity  or  beneath  the  skin  as  large  tumor  masses;  they  are 
also  frequently  met  in  the  neighborhood  of  the  jaw  and  thyroid 
gland,  originating  from  remnants  of  the  branchial  cartilages,  in 
goats,  horses,  dogs  and  cattle.  /\s  mixed  growths  (chondro- 
adenoma)  they  have  been  seen  a  number  of  times  in  the  lungs, 
mammary  gland  and  in  the  testicles  in  animals.  As  exceptionally 
rare  instances  may  be  mentioned  enchondromata  of  the  vitreous 


Osteoma.       ■  353 

humor  of  both  eyes  in  a  cong-enitally  blind  colt  (Renner),  and 
a  chondroma  the  size  of  a  fist  in  the  wall  of  a  calf's  stomach 
(first  stomach). 

A  chondroma  should  be  looked  ujjon  as  a  dan.ijerons  growth, 
at  times  because  of  the  position  it  may  occupy,  but  also  because 
of  its  usual!}-  marked  tendency  to  grow  large,  and  further  because 
it  can  give  rise  to  metastasis.  The  cartilaginous  masses  hap- 
pening to  penetrate  by  growth  into  the  veins  sometimes  develop 
long  processes  within  the  lumen  of  the  vessels,  which  are  of 
course  obstructed;  and  any  little  portions  which  luay  be  carried 
awav  bv  the  blood  may  form  metastatic  nodes  in  other  organs. 

In  man  there  are  seen  from  time  to  time  pea-sized  growths  of  cartilag- 
inous tissue,  peculiar  in  the  marked  vacuolation  of  their  cells  and  in  their 
gelatinous  consistence,  at  the  base  of  the  skull  in  the  neighborhood  of  the 
spheno-occipital  suture;  these,  because  of  the  bladder-like,  swollen  character 
of  the  cells,  were  formerly  known  as  cccliondromafa  physaliformia,  but  are 
recognized  to  be  remnants  of  the  notochord  and  are  called  chordomata. 

Osteomata. 

Bv  the  term  osteoma  or  bone  tumor  is  meant  a  definite  new 
formation  presenting  the  structure  of  bone  tissue  and  its  mar- 
row. According  to  the  density  of  the  calcified  bone  substance 
there  are  distinguished  (i)  the  cbiiniatcd  osteoma  (osteo))ia 
chur Ileum  )  which  is  of  ivory-like  hardness  like  the  dense  cortical 
bone;  (2)  the  spongy  osteoma  (osteoma  spongiosum),  of  a  more 
cancellous  t}pe,  containing  considerable  marrow  substance ;  and 
(3)  the  meduUar\  osteoma  (osteoma  medullosum)  composed 
principallv  of  marrow.  In  most  instances  the  structure  of  the 
bone  (calcified  matrix  in  lamellar  arrangement  about  Haversian 
canals,  bone  corpuscles  in  lacunre.  bloodvessels,  marrow  cells 
and  fat)  is  characteristic;  but.  often  as  far  as  the  marrow  is 
concerned,  abnormalities  are  common,  the  medullary  spaces  being 
occupied  perhaps  rather  by  spindle  cells  and  fibrous  connective 
tissue  (osteofibroma)  or  showing  ^-^pecial  abundance  of  round  cells 
and  giant  cells  (osteosarcoma).  Where  the  bone  trabecula  have 
no  lamellated  structure  and  the  bone  corpuscles  do  not  show 
the  usual  projecting  branches  the  specimen  is  spoken  of  as  an 
osteoid  sarcoma. 

In  manv  cases  it  is  dif^cult  and  even  impossible  to  determine 
whether  a  tumor-like  osseous  groAvth  is  really  of  autoblasto- 
matous  origin  or  is  the  product  of  inflaiumatory  proliferation, 
because  definite  lines  of  separation  between  the  two  cannot  be 


354  Tumors. 

drawn.  For  this  reason  visually  only  the  more  massive,  large  and 
clearly  defined  bony  growths  are  called  osteomata,  and  the  rest 
are  known  collectively  as  ostcopJiytcs.  The  small  protuberances, 
of  the  size  of  a  pea  to  that  of  a  nut,  projecting  from  the  surface 
of  bones,  are  also  called  c.rosfoscs ;  the  flat  superficial  thickenings 
around  bone  shafts,  periostoscs;  those  which  grow  along  bones 
as  bony  formations  in  fasciae  and  connective  tissue,  parosloses; 
an  ivory-like,  hard,  well-defined  formation  in  the  interior  of 
bones,  an  cnostosis.  Dififuse  thickenings  of  the  bones  in  the 
skeleton  from  osseous  hyperplasia  are  known  as  hyperostoses; 
osteophytes  with  cartilaginous  coverings,  as  cartilaginous  osteo- 
phytes. 

The  osteophytes  and  osteomata  growing  from  the  skeleton 
develop  principally  from  the  osteoblastic  layer  of  the  periosteum 
or  from  cartilaginous  developmental  bases  (aulage)  ;  some  are 
congenital  or  from  their  position  may  be  looked  upon  as  caused 
b\'  disturbances  of  embryonal  development  and  as  referable  to  in- 
clusive misplacement  of  bits  of  the  embryonic  bone  tissue  af- 
fected. This  view  is  especially  applicable  to  the  rather  common 
large  osteomata  of  the  head  cavities  (cattle,  horses),  arising  from 
the  sphenoid,  ethmoid  or  the  turbinate  bones ;  in  their  gradual 
enlargement  they  press  upon  the  surrounding  bony  walls,  force 
the  jaw  and  nose  out  of  position,  project  into  the  maxillary  sinus, 
nasal  cavities  or  into  the  orbit  or  cranial  cavity,  and  obstruct 
these  spaces  with  continuous  pressure  upon  the  respective  soft 
parts.  Other  forms  which  are  located  on  the  outside  of  bones, 
sometimes  as  broad  expanded  growths  or  arising  from  slender 
pedicles,  probably  are  caused  by  traumatic  influences ;  and  the 
exostoses  which  are  met  commonly  in  the  under  jaw  of  the  horse 
apparently  arise  from  isolated  osteoplastic  foci ;  and  the  large 
osteomata  on  the  horn  process  in  cattle  are  probably  due  to  loss 
of  tissue  tension  caused  by  injur}-  to  the  horn  capsule. 

A  remarkable  variety  of  pathological  bone  proliferation  is  the 
progressive  osteitosis  met  ^^•ith  in  young  dogs.  It  consists  in 
the  occurrence  of  bone  formation  at  the  places  of  attachment 
of  the  tendons  and  muscles  of  the  lower  jaw  and  extremities, 
causing  as  it  progressively  advances  an  atrophy  of  the  muscles 
and  giving  the  animal  a  stifif  awkward  gait :  it  is  accompanied 
by  marked  thickening  of  all  the  bones  of  the  skeleton.  The 
disease  is  similar  to  the  aft'ection  in  man  known  as  myositis 
ossificans  progressiva,  and  is  apparently  an  abnormality  of  de- 
velopment, in  which    as    Ribbert    supposes    the    intermuscular  con- 


Osteoma. 


355 


nective  tissue  acts  as  a  derivative  of  the  periosteum.  In  fresh 
specimens  the  periosteum  and  muscular  connective  tissue  of 
these  cases  appear  to  be  merged  into  one  mass  of  bacony,  cartila- 
ginous and  rigid  character;  after  maceration,  brittle,  papyraceous 


Fig.  05. 
Osteoma  on  the  horn  process  of  a  cow. 

and   gland-like   plaques   and   nodosities   of  bone   are    found   along 
the  muscular  attachments. 

Osseous  growths  of  irregular  and  flat  shape  {ossiUcatio 
raconosa,  plana)  and  intermediate  types  approaching  compact 
osteomata  have  been  encountered  as  isolated  deposits  and  in  combi- 
nation with  cartilage  and  fibrous  tissue  occasionally  in  the  lungs 
(cowO,  peritoneum  and  mesentery  (cow,  hog,  dog),  upon  and 
within  the  udder  (cow%  dog),  testicles  (horse),  in  the  vitreous 
humor  of  the  e}'e  (horse),  and  in  the  right  cardiac  auricle  of  the 
horse.     The  attempt  to  explain  the  origin  of  these  bone  forma- 


Fig.  96. 
Section  of  above  osteoma  of  horn  process. 


tions  must  rest  with  the  assumption  of  the  possibility  of  a  meta- 
plasia of  fibrillar  connective  tissue  into  a  calcified  matrix,  with 
transformation  of'the  connective  tissue  corpuscles  into  bone  cor- 
puscles. 


356  Tumors. 

Myomata. 

A  myoma  or  muscle  tissue  tumor  is  composed  of  muscle 
fibres,  together  with  an  accompanying  vascular  connective  tissue. 
Corresponding  with  the  two  varieties  of  muscle,  these  tumors 
occur  in  two  forms,  one,  the  leiomyoma  {myoma  IccviccUulai'c), 
composed  of  smooth  muscle  cells,  and  the  other,  rhabdomyoma 
{myoma  striocellularc) ,  a  tumor  made  up  of  transversely  striated 
fibres. 

The  latter  {rhabdomyoma)  is  a  very  rare  tumor;  and  never 
shows  the  muscle  tissue  in  a  state  of  perfect  development  like 
that  of  the  muscles  of  the  body.  The  muscle  fibres  are  rather  of 
an  embrvonic  type  and  are  usually  mingled  with  embryonic  con- 
nective tissue  {rhabdomyosarcoma,  rliabdomyoma  sarcomatodes) 
or  combined  with  glandular  tissue  in  addition  {rJiabdomyoaden- 
osarcoma).  The  muscle  fibres  are  thinner  than  normally, 
ribbon  shaped  ;  their  transverse  striae  are  not  complete  and  are  only 
apparent  along  the  edges  of  the  fibres,  a  richly  nucleated  sarco- 
plasm  occupying  the  interior  of  the  fibres.  Numerous  spindle 
cells  with  longitudinal  striations  may  be  noticed  in  addition, 
which  may  be  looked  upon  as  early  stages  or  as  muscle  fibres  per- 
sisting in  undeveloped  condition.  These  muscle  elements  are  not 
arranged  in  compact  parallel  bundles  but  are  scattered  about  in 
irregular  manner.  They  are  therefore  not  of  as  deep  red  a  color 
as  normal  striated  muscle,  having  rather  a  pale  reddish-gray 
tint.  Thev  occur  as  more  or  less  well  defined  nodes  ;  and  rarely 
occur  in  situations  where  striated  muscle  tissue  exists  normally 
but  rather  in  complete  heterotopism,  in  organs  which  have  no 
such  basic  elements.  This  would  indicate  that  rhabdomyomata 
originate  in  muscle  germinal  tissue  misplaced  in  embryonal  life. 
This  is  doubtless  true  of  the  tumors  in  question  Avhich  develop 
from  the  kidney,  the  muscular  elements  in  their  structure  appa- 
rently originating  from  misplaced  portions  of  the  myotomes  of 
the  primitive  vertebral  column.  Johne  has  recorded  an  adeno- 
sarco-rhabdomyoma  of  this  type  from  the  kidney  (hog)  which 
weighed  fourteen  kilograms.  (In  man  rhabdomyomata  have 
been  recognized  frequently  in  the  kidneys,  testis,  uterine  wall, 
urinary  bladder  and  the  oesophagus.)  Besides  the  case  above 
mentioned,  contributed  by  Johne,  there  are  only  two  instances  of 
rhabdomyomata  in  animals  recorded  in  literature  (Casper).  One 
was  observed  by  Gratia  in  an  old  horse  in  a  dissecting  room,  a 
fusiform  tumor  about  eight  or  ten  centimeters  in  length,  in  the 


Myoma,  357 

vagus  nerve  trunk  abont  the  middle  c)t  the  neck;  the  other  was 
found  by  Kolessnikow,  growing  in  the  tail  and  perianal  con- 
nective tissue  of  a  twenty-year-old  stallion,  a  tumor  containing 
pigment  cells  {rhabdoniyosarcoina  melanodes),  which  had  given 
rise  to  numerous  metastases  in  the  liver,  spleen,  peritoneum  and 
pleura. 

The  Icioiiiyoina  is  found  more  frequently  and  in  easily  recog- 
nized forms  in  animals:  in  case  of  extensive  combination  with 

if.  f  >  t«-  "^ 


/ 


^*-%«- 


^*«» 


Fig.  97. 

Leiomyoma  (from  utei-us)  :  «.  ijlace  shuwlng  buadle  of  muscle  fibres  cut   transversely. 

tibrous  connective  tissue,  as  may  sometimes  be  seen,  the  growth 
is  spoken  of  as  a  myofibroma.  These  tumors  always  develop 
in  a  structure  rich  in  smooth  muscle,  and  are  consequently  met 
principally  in  the  muscular  wall  of  the  uterus  and  vagina  (in  cow 
and  hog,  less  frequently  in  the  dog),  of  the  intestine  and  stomach 
(horse),  urinary  bladder  (dog),  now  and  again  in  the  testis 
(horse),  and  in  the  subcutaneous  tissue  (horse).  They  are 
rounded  or  globular,  firm  tumor  masses,  which  are  sometimes 
found  projecting  from  their  places  of  origin,  covered  over 
smoothly  with  mucous  or  serous  membrane,  presenting  on  their 


358  Tumors. 

cut  surface  a  fibrous  or  striated  appearance,  of  a  reddish-gray  or 
pale  gray  color.  Especially  the  leiomyomata  growing  from  the 
uterus  and  hanging  to  this  organ  in  the  peritoneal  sac,  may  attain 
enormous  size,  possibly  as  large  as  a  well  filled  horse's  stomach, 
weighing  from  thirteen  to  thirty-six,  to  one  hundred  kilograms. 

The  smooth  muscle  fibres,  easily  recognized  by  their  long 
fusiform  shape  and  rod-shaped  nuclei,  are  arranged  parallel  to 
one  another  in  bundles  interlacing  in  every  direction  with  each 
other  in  confused  manner.  In  sections  the  fascicles  are  found 
cut  longitudinally,  obliquely  and  transversely,  and  between  these 
the  vascular  connective  tissue  may  be  'observed  in  variable 
amount  as  clearer  threads.  In  pedunculated  examples  where  the 
myomata  have  in  consequence  been  subject  to  twisting,  circu- 
latory disturbances  are  often  determined,  as  results  of  which 
congestive  haemorrhages,  cedematous  appearance,  anaemic  necroses 
and  fatty  degeneration  may  take  place  in  the  tumor  mass. 

In  man  epithelial  inclusions  and  hollow  tubules  have  been 
noted  in  the  myomata  of  the  genital  organs,  this  histological 
feature  giving  support  to  the  view  that  the  myoma  in  this 
situation  is  related  to  embryonal  disturbances  which  have  occa- 
sioned misplacement  and  isolation  of  portions  of  the  Wolffian 
body  or  of  the  Miillerian  ducts   (adenomyomata). 

Leiomyomata  are  usually  single  primary  growths  [in  human 
beings  they  are  often  multiple],  and  give  rise  to  harm  only 
by  their  volume.  They  are  not  recurrent  tumors  [and  are  not 
metastatic] 

Neuromata   and   Gliomata. 

A  neuroma,  or  nervous  tissue  tumor,  strictly  speaking  must 
be  made  up  of  nerve  fibres  or  gangliomic  cells  in  luxuriant  prolif- 
eration, accompanied  by  a  supporting  framework  and  by  bloodves- 
sels. If  we  exclude  the  terminal  thickenings  of  nerve  stumps 
occasionally  occurring  after  neurotomy,  the  so-called  amputation 
neuromata  (v.,  p.  250),  from  the  list  of  true  tumors  (because  their 
growth  ceases  after  a  time),  it  may  be  said  that  the  formation  of 
true  neuromata  in  animals  has  as  yet  never  been  certainly  proved 
to  occur.  Even  in  man  but  few  instances  of  this  type  of  neoplasm 
are  known,  situated  in  the  sympathetic  area  (especially  coeliac  gan- 
glion and  pelvic  plexus),  as  nodes  ranging  up  to  the  size  of  a 
child's  head. 

The  growths  summarily  designated  by  the  name  neuroma  in 


Neuroma. 


359 


the  literature  are  nenrofihromata  and  neuromyxomata,  tumors 
which  develop  in  corded,  fusiform  or  cylindrical  thickenings  up 
to  the  size  of  a  finger,  or  in  nodular  shape  up  to  the  size  of  a 


Fig.  98. 
Neuroflbromatosis   of   bi-achial    plexus   of    cow. 

potato,  on  the  nerve  trunks.  Their  formation  results  from  a 
marked  proliferation  of  the  -perineural  connective  tissue  and 
nerve  sheath  about  the  nerve  fibres.    The  proliferated  mass  has 


360  Tumors. 

a  grayish-red,  seniitransparent  appearance  and  usually  extends 
along  many  adjacent  nerves  as  a  nerve  plexus,  giving  rise  to 
an  extensively  intertwining  growth  { plcxiform  or  vine-like  neuro- 
fibroma). Tumors  of  this  kind  have  been  observed,  especially  in 
cattle,  involving  the  brachial  plexus  and  the  dorsal,  costal  and 
sternal  nerves  (Ostertag,  Alorot,  Blanc,  author's  personal  obser- 
vation), and  producing  in  these  structures  hundreds  of  nodular 
thickenings.  Morot  counted  in  one  case  thirteen  hundred  and 
fifteen  neuromyxomata  in  an  old  cow  and  traced  them  even  to 
the  nerves  of  the  pharynx  and  heart.  Leisering  observed  similar 
growths  in  a  horse  with  extensive  involvement  of  a  number  of 
nerve  trunks. 

An  embryonic  developmental  disturbance  of  unknown  nature 
has  been  regarded  as  the  basic  factor  for  the  neurofibromata  and 
neuromata  observed  in  man,  because  the  growths  have  been  met 
as  congenital  and  inherited  faults. 

Glioma  or  ncuro glioma,  the  tumor  of  nervous  connective  tis- 
sue substance,  is  produced  by  proliferation  of  the  glia  cells  of  the 
central  nervous  system  or  the  granular  layer  of  the  retina  of  the 
eye,  and  occurs  primarily  only  in  these  two  positions.  In  animals 
it  has  been  recognized  with  certainty  but  twice,  once  by  Gratia 
in  a  dog's  brain  (ganglion  Gasseri)  and  again  by  Piana  in  the 
spinal  cord  of  a  dog,  in  both  instances  causing  palsies  from 
pressure  upon  the  central  nervous  substance  and  the  emerging 
trunks. 

The  gliomata  of  the  human  brain  are  usually  embedded  in 
the  brain  tissue  without  sharp  definition  from  the  latter  and  are 
so  merged  with  it  that  they  are  only  recognizable  as  diffuse 
grayish  or  reddish  firm  areas.  They  are  made  up  of  protoplasmic 
cells  with  numerous  fibrils  projecting  in  a  radiating  fashion  from 
all  sides  of  the  cell  (spider  cells,  astrocytes)  ;  and  in  this  fibrillar 
meshwork  there  are  in  some  instances  also  present  polymor- 
phous sarcomatous  or  ganglionic  cells,  and  epithelial  inclusions 
may  be  observed  (spaces  lined  with  cylindrical  epithelium).  This 
last  feature  and  the  occurrence  of  these  growths  in  newly  born 
children  confirm  the  belief  that  disturbances  of  development  of 
the  cerebral  vesicles  are  the  basis  of  these  neuroglia  growths,  for 
example  isolation  of  offshoots  from  parts  covered  by  ependyma 
(perhaps,  too,  transformation  of  the  glia  cells  to  embryonic  cel- 
lular type,  the  glia  tissue  being  originally  an  epithelial  tissue 
differentiated  into  a  supporting  material). 


Cliunia.  3^1 

Retinal  gliomata  of  man  spread  out  as  grayish  nodular  tumors 
over  the  inner  surface  of  the  globe  of  the  e\e,  but  are  also  met  per- 
forating the  sclera,  growing  along  the  optic  nerve  and  perhaps  es- 
caping into  the  orbit ;  they  occur  as  congenital  growths  sometimes 
involving  both  eyes,  and  have  been  observed  in  a  few  instances  in 
several  children  of  the  same  parents.     For  these  reasons  and  be,- 
cause  of  their  structure  they  may  invariably  be  referred  for  their 
origin  to  developmental  faults.    They  are  only  in  part  composed 
of  glia  tissue,  being  principally  made  up  of  neural  epithelium  of 
the  retina  reverted  to  embryonal  type,  arranged  in  thick  sheath- 
like layers  around  the  synchronously  proliferating  bloodvessels. 
[These  so-called  retinal  gliomata  are  the  subject  of  considerable 
controversy.     The  presence  of  any  true  glia  tissue  comparable 
to  that  of  the  brain  is  in  itself  questionable,  and  the  evident  part 
taken  by  the  retinal  neuroepithelial  tissues  has  led  to  their  being 
denominated  neuroepitheliomata.    These  neuroepithelial  cells  are 
frequently  found  in  a  so-called  rosette  arrangement,  as  the  cylin- 
drical epithelium  seen  in  sections  of  small  ducts.     The  tumor  in 
its  infiltrating  and  metastatic  character  is  a  very  different  growth 
from  the  glioma  of  the  brain  ;  the   former  is  rapidly   fatal,   while 
the  latter    shows    little    tendency  lieyond  a  slow  peripheral  infiltra- 
tive enlargenient  to  extend,  and  persons  may  have  harbored  these 
growths  for  years  with  little  definite  evidence  of  their  presence. 
The  more  separate  arrangement  of  the  cells  of  the  true  glioma, 
the  branching  fibrils  of  the  cells  preventing  close  adjustment,  is 
not  seen  in  the  retinal  glioma,  whose  cells  are  very  closely  packed  and 
evidently  have  but  few^  and  insignificant  projections  upon  them 
(in  fact   one   must  examine  with   great  care  even   after  special 
staining  to  think  that  these  projections  exist  in  any  comparable 
degree).     The  editor  would  regard  favorably  the  separation  of 
these   growths   from  the   class  of  true  gliomata,   preferring  the 
more  distinctive  and  well  justified  term  of  neuroepithelioma. 

The  true  glioma  of  the  brain  is  usually  single;  sometimes  sev- 
eral have  been  found,  usually  in  close  relation  and  probably  in 
reality  representing  the  same  growth.  A\hen  pure  and  free  from 
sarcomatous  combination  the  tumor  should  be  regarded  as  rela- 
tively benign  save  for  its  pressure  effects.  Distant  metastasis  is 
rare;  although  local  metastasis  from  peripheral  infiltration  is 
the  rule.] 


362 


Tumors. 


Haemangiomata  and  Lymphangiomata. 


The  hccmaugioiiia,  or  blood  vessel  tumor,  is  made  up  of  dis- 
tended and  proliferated  vascular  tubes  filled  with  blood,  together 
with  the  connective  tissue  supporting  these  vessels.  Strictly  speak- 
ing, a  true  vessel  tumor  must  consist  for  the  most  part  at  least  of 
vessels  which  have  been  newly  formed,  and  should  not  be  a  tumor- 
like enlargement  made  up  simply  of  pre-existing  vessels  Avhich 
have  become  enlarged  from  some  pathological  cause.  It  is,  how- 
ever, difficult  to  make  a  distinction  between  these  two  conditions, 
partly  possible  only  by  examination  of  microscopic  sections.  There- 
fore in  a  gross  anatomical  sense  there  is  usually  included  under  the 
term  hsemangioma,  in  a  tentative  way,  a  second  variety  which  is 
made  up  of  blood  lacunae,  which  give  rise  to  a  nodular  irregularity 
in  shape  and  a  spongy  consistence  of  the  part  affected  [caz'ernous 
hcemangionia] . 


Fig.  t)!). 
Portion  of  cavernciis  angioma  of  cow,  seat  of  multiple  thrombi. 

In  man  hsemangeiomata  are  represented  first  by  the  invariably 
congenital  blood-red  or  bluish-red,  sharply  outlined  areas  of  skin, 
in  which  the  tissue  of  the  cutis,  often  to  the  depth  of  the  sub- 
cutaneous fat,  is  filled  completely  with  thin-walled  bloodvessels  in 
a  definitely  limited  area  {Hccniangioma  teleangicctaticum,  ncc- 
z'lis  vascnlosus,  Hammcus,  vinosiis,  wine  mark). 

Such  independent  vascular  tumors,  caused  by  a  disturbance  of 
tissue  development,  are,  it  appears,  but  rarely  met  in  animals,  prob- 
ably because  the  pigment  and  hair  of  the  skin  conceals  their  pres- 
ence. However,  Leisering  observed  an  angioma  as  large  as  a  hen's 
&gg  in  a  dog,  in  the  subcutaneous  tissue  (under  surface  of  the  tail)  ; 
Siedamgrotzky  a  similar  one  in  a  poodle,  showing  as  a  bluish-black 
area  through  the  skin ;  Bonnet  a  fibroangioma  as  large  as  a  child's 
head  with  a  strong  connective  tissue  stroma  in  a  horse,  in  the  papil- 


Hcsmangioma. 


363 


lary  bodies  of  the  root  of  the  tcail.  Similar  teleangiectases  are  more 
frequently  recorded  as  occurring-  in  the  nasal  septum  in  the  horse 
(Liipke,  Hofmann,  Diegendesch,  et  al),  appearing  as  superficial 
red  or  bluish-red,  smooth,  easily  bleeding  areas. 

The  very  common  capillary  teleangiectases  in  the  bovine  liver, 
multiple  purplish-red  or  Ijluish-rcd  spots  showing  through  the  Glis- 
sonian  capsule,  and  appearing  as  finely  spongy,  bloody  areas  in 
section,  are  to  be  regarded  according  to  the  studies  of  Stroh  as  due 
to  passive  hyperaemia  (pressure  by  the  paunch  in  tympanites). 

The  second  type  of  angioma  above  mentioned  is  the  cavernous 
angioma  of  the  human  liver,  occurring  in  similar' forms  in  the  cow 
and  horse.     A  system  of  blood  spaces  is  formed  in  the  liver,  com- 


r' 


/ 


V 


^ 


^ 


(1 

H 


:,.^)Ki' 


■w^ 


^-^^■ 


Fig.  100. 
Portions  of  an  angiomatous  liver   of  a  horse. 

parable  to  the  erectile  tissue  of  the  penis  or  to  coarse  sponge,  with 
cavernous  passages  of  very  irregular  width  and  varicose,  interrupted 
by  projecting  ledge-like  bands  of  connective  tissue.  The  area,  recog- 
nizable from  the  external  surface  by  the  superficial  dark  red  eleva- 
tions and  the  increased  volume  of  the  involved  lobe  of  the  liver,  is 
not  sharply  outlined,  and  contains  quantities  of  tarry  blood  and  fre- 
quently also  firm  laminated  clots.  Between  the  connective  tissue 
septa  islets  of  liver  structure  sometimes  persist.  The  whole  appear- 
ance gives  one  the  impression  of  a  bunch  of  distended  veins,  dilated 


VERSITY  J 


OF 


364 


Tumors. 


from  passive  congestion,  or  a  nodular  h£emorrhagic  focus,  rather 
than  of  a  neoplasm.  In  man,  however,  such  foci  have  been  ob- 
served in  congenital  occurrences ;  and  Ribbert  suspects  as  the  fun- 
damental cause  some  developmental  disturbances  of  the  affected 
part  of  the  liver. 

The  name  lymphangioma,  or  lymph  vessel  tumor,  is  applied  to 
congenital  tumors  in  man,  which  occur  as  independent  bunches  of 
lymph  vessels  (that  is,  not  in  direct  relation  with  the  lymph  vessels 


Fig.  101. 

Cavernou.s   angioma  :    0,   lacuna   filled   with   blood  ;    h,   indurated   intervascular 

connective   tissue. 


of  the  adjacent  tissues).  They  are  especially  seen  in  the  neck,  in 
the  mesentery,  the  lips  and  the  genital  organs,  sometimes  not  well 
defined  and  causing  rather  a  diffuse  swelling  of  the  part.  They  are 
made  up  of  channel-like,  anastomosing,  multiloculated  passages 
filled  with  lymph,  their  walls  of  fibrous  tissue  lined  with  endothe- 
lium. 

There  is  only  one  definite  and  certain  record  of  the  occurrence 
of  tliis  type  of  tumor  in  animals,  published  by  H.  Markus  ;*  on  the 

*  Monatsheft  f.  pr.  Tierlieilk.     Stuttgart,  1902,  p.   185. 


Lyiiipliaiigioiiia ;  Sarcoma.  365 

costal,  pulmonary  and  pericardial  pleura  of  a  horse  there  were  found 
numerous  superficial,  vesicular  growths  from  the  size  of  a  pin's  head 
to  that  of  a  nut  or  pigeon's  egg,  some  with  broad  surface,  others 
pedunculated,  exuding  a  serous  fluid  on  section  from  the  spongy 
tissue.  Microscopically,  they  consisted  of  a  loculatcd  connective 
tissue  framework,  the  spaces  lined  with  endothelium  and  containing 
scattered  l\niph  cells.  The  growth  was  entirely  local,  the  lymph 
glands  not  afifected. 

Schindelka  observed  in  a  cat  as  an  anomah',  perhaps  of  tlii^  same 
categorj',  a  number  of  tumors  about  all  the  nipples,  ranging  in  size  from 
that  of  a  hazel  nut  to  that  of  a  hen's  egg.  encircling  the  nipples  and  hang- 
ing loosely,  filled  with  fluid  and  fluctuating  like  a  leather  bottle  when 
handled ;  firm  lymph  cords,  of  the  thickness  of  the  little  finger  and  varicose, 
branched  out   from  these  formations   into  the   skin. 

Now  and  dien  large,  tortuous  lymph  vessels  filled  with  lymph  are  found 
in  the  horse  in  the  heart  or  mesentery,  which  are,  however,  merely  lymph- 
angiectases. 

Sarcomata. 

The  name  sarcoma  (o-dp^.  Hesh;  fleshy  ttimor,  from  its  similarity 
to  proud  flesh  or  exuberant  granulation  tissue)  was  applied  by  \'ir- 
chow  to  those  connective  tissue  tumors  which  do  not  possess  the 
definitive  characteristics  of  a  fibroma,  chondroma,  lipoma,  etc.,  that 
is,  which  are  not  composed  entirely  of  matttre  fibrous  tissue,  carti- 
lage, bone,  etc..  btit  throughout  their  continuous  growth  are  made 
up  of  cells  of  the  connective  tissue  group  persisting  in  their  embry- 
onic characters.  They  are  new  growths  whose  tissue  shows  no 
tendency  to  maturation  and  is  composed  principally  just  as  in 
embryonic  life  of  undifterentiatcd  mesoblastic  cells  and  scanty  in- 
tercellular substance,  and  whicli  are  distinguished  from  the  simple 
connective  tissue  tumors  particularly  b\-  thc'r  malignant  character, 
their  rapid  and  destructive  growth,  their  tendency  to  recurrence 
after  removal   and  their  formation   of  metastases. 

The  sarcomata  are  classified  from  two  standpoints :  first,  from 
the  predominating  t\pe  of  the  cells  of  the  growth ;  and  second, 
from  the  admixture  of  mature  tissue  with  the  embryonic  cells. 

Many  sarcomata  are  characterized  by  a  special  predominating 
tvpe  of  cell ;  and  although  the  shape  of  a  cell  does  not  alone  deter- 
mine the  character  of  a  tumor,  the  tissues  of  origin  and  the  nature  of 
growth  being  also  taken  into  consideration,  it  gives  the  microscopic 
picture  of  a  tumor  an  individuality  of  importance  in  nomenclature, 
and  characteristic  because  of  the  deficiency  of  fully  mattered  types  oi 


366 


Tumors. 


tissue.  Those  forms  of  sarcoma  whose  cells  do  not  grow  with  any 
special  uniformity,  but  rather  as  a  motley  mass  of  various  forms  in 
atypical  embryonal  proliferation,  cannot  of  course  be  named  from 
the  cellular  character.  These  instances,  as  a  rule,  represent  the 
malignant  form  of  fibroma,  chondroma,  osteoma  or  melanoma,  or 
are  mixed  tumors ;  in  these  cases  a  combined  expression  is  used. 
The  completely  developed  tissue  forms,  as  it  were,  the  framework  or 
stroma,  and  the  cells  the  parenchyma. 


(@ 


g/»*  ^®  J    


.%.. 


V   i 


3^ 


•  t%r^ 


■^:.;''"^c>5  7 


Fig.   102. 
Alveolar  round  cell  sarcoma,  from  testicle    (human). 


The  principal  types  of  sarcoma  may  be  divided  as  follows : 
A — Cellular  Sarcomata:  the  round  cell  sarcoma,  spindle  cell  sar- 
coma, giant  cell  sarcoma,  stellate  cell  sarcoma,  polymorphocellular 
sarcoma. 

B — Combined  Sarcomata:  the  fibrosarcoma,  liposarcoma,  chon- 
drosarcoma, osteosarcoma,  myxosarcoma,  myosarcoma,  gliosarcoma, 
lymphosarcoma,  melanosarcoma. 

In  stricter  application  it  would  be  well  to  determine  precisely,  as  Borst 
and  Diirk  have  urged,  whether  the  embryonal  cells  were  present  from  the 


Sarcoma.  367 

beginning,  and  their  proliferation  and  that  of  the  mature  types  of  cells 
have  from  the  first  developed  side  by  side,  or  whether  a  simple  tumor 
originally  existed  and  later  assumed  a  typical  growth  from  changes  in  the 
cellular  proliferate.  In  the  former  case  the  combined  types  of  tissue  may 
lie  indicated  l)y  the  use  of  two  nouns  (as  fibro-sarcoma)  ;  in  the  latter 
.by  the  adjective  prefix  "sarcomatous"  [the  change  into  sarcomatous  type 
may  be  expressed].  In  the  course  of  clinical  observations,  where  the 
succession  of  various  features  is  recognizable,  such  distinctions  may  be  occa- 
sionally made ;  but  in  purely  anatomical  considerations  they  cannot  be  made. 


Fig.  103. 

Spindle   cell    sarcoma,    from    periosteal    origin :    a,    transverse    section    of    hnnrlle    of 
splndlo  cells  ;  b,  capillary  blood  vessel. 

The  round  cell  sarcoma  (sarcoma  globocclliihirc)  consists  either 
of  cells  of  the  appearance  of  lymphocyteSj  small  round  elements  with 
narrow  cytoplasm  and  granttlar  nucleus  (small  cell  sarcoma),  or  of 
large  round  and  polymorphous  cells  (large  cell  sarcoma),  closely 
packed  together  and  with  such  a  small  amount  of  fibrillar  intercellu- 
lar substance  that  the  cells  are  but  loosely  attached.  The  tumor 
has  a  very  soft  consistence  and  is  of  a  grayish  to  a  grayish-red 
color.  When  the  supportive  tissue  enclosing  the  round  cells  is 
arranged  in  a  reticular  manner,  forming  a  fine  fibrillar  meshw^ork, 
and  the  tumor  has  originated  from  one  of  the  lymphatic  structures 


368  Tumors. 

(spleen,   lymph  glands,  bone   marrow),  it  is  known  as  a  lympho- 
sarcoma. 

The  spindle  cell  sarcoiiia  (sarcoma  fnsiccUidarc)  also  presents 
both  small  and  large  cellular  elements  and  originates  from  ordinary 
connective  tissue.  Its  spindle  shaped,  more  or  less  elongated  cells 
contain  one  or  more  round  to  fusiform  nuclei,  are  placed  parallel 
to  each  other,  arranged  along  the  bloodvessels  in  bundles  inter- 
twining in   different   directions,   and  are  comparable   to  the  fibro- 


id u- 


Fig.  104. 

(jlant    cell    sarcoma,   from    human    jaw :    a,   capillary    blood    channel  :    h,    giant    cell ; 
c,   sarcomatous   cells,   In    this    specimen   of   spindle   type. 

blasts  of  granulation  tissue.  The  bloodvessels  are  also  of  em- 
bryonic type,  persisting  as  simple  endothelial  channels,  often  distin- 
guishable from  lymph  spaces  merely  by  the  fact  that  they  contain 
red  blood  cells.  Where  the  intercellular  fibrillar  substance  is  more 
prominently  developed  the  spindle  cell  sarcoma  becomes  a  fibro- 
sarcoma. 

The  giant  cell  sarcoma  (sarcoma  gigantocelhdarc).  The  pres- 
ence of  numerous  giant  cells  in  a  connective  tissue  tumor,  always 
a  striking  feature  of  the  microscopic  sections,  gives  origin  to  the 
term  giant  cell  sarcoma.    The  large  polynucleated  cells  thus  known 


Sarcojiia.  369 

are  usually  derivatives  of  the  marrow  or  periosteum  where  they 
occur  normally    (known  as   myeloplaxes).      They   differ  from   the 
degenerative  types  of  giant  cells    (formed  in  tubercles  and  about 
foreign  bodies)   in  the  fact  that  their  nuclei  are  not  located  about 
the  periphery  but  are  scattered  well  .in  the  interior  and  all  through 
the  cell  protoplasm ;  but  all  sorts  of  variations  may  be  found  (com-  . 
pletely  divided  or  wreath-like  clumping  of  the  nuclei,  giant  nuclei, 
eccentric  dividing  forms,  budding  nuclei).     The  number  of  nuclei 
in  one  cell  may  reach  not  merely  a  dozen  or  two,  but  hundreds. 
The  cells,  whose  dimensions  may  exceed  ten  to  thirty  times  that  of 
a   white   blood   corpuscle,   are   irregularly   rounded,   their   margins 
jagged,  are  flattened  out  like  large  fibroblasts  and  are  often  vacuo- 
lated with   fat  droplets.     In   addition   to  the  giant  cells  there  are 
usually  numerous  round  and  spindle  shaped  cells  in  the  tumor,  and 
a  rich  supply  of  capillary  vessels  from  which  blood  extravasations 
are   frequently   found   in   the  tissue,   and  which   give  the   tumor  a 
dark-red   or   brownish-red    color.      From    its    medullary   origin   the 
giant  cell  sarcoma  is  often  called  a  iuycIoi:;ciious  sarcoma  or  111  ye- 
loma;  and  when  a  homogeneous  intercellular  substance  is  present, 
becoming  calcified  and  forming  cartilaginous  islands  or  bony  tra- 
becula.  the  combined  appearances  are  denoted  by  the  terms  osteoid 
sarcoma  and  osteochondrosarcoma. 

The  stellate  or  reticular  cell  sarcoma  (sarcoma  sfellocelluhve) 
is  characterized  by  highly  branched  cells  forming  an  intricate  mesh- 
work,  usually  enclosing  between  their  projections  a  mucoid,  glass- 
like intercellular  material,  giving  to  the  growth  characteristics 
commonly  indicated  by  the  term  myxosarcoma. 

The  polvmorphoeellular  sarcoma  (sarcoma  mi.vfoccllulare)  is  a 
name  given  to  tliose  connective  tissue  tumors  whose  cellular  con- 
stituents follow  no  one  cellular  form,  but  are  made  up  of  a  con- 
fused mixture  of  round,  spindle,  stellate  and  giant  cells,  or  the  bulk 
of  whose  cells  are  elements  of  variable  form,  irregularly  polygonal, 
enclosed  in  a  comparatively  small  amount  of  intercellular  matrix. 

The  morphological  appearance  of  sarcoma  cells,  the  size  and 
polygonal  shape  of  their  cellular  substance  and  their  alveolated 
arrangement  make  it  often  very  difficult  to  determine  to  which  of 
the  classes  of  sarcomata  described  and  specially  named  by  differ- 
ent authors  a  given  sarcomatous  neoplasm  should  be  referred. 
This  difficulty  and  the  lack  of  finality  in  our  histogenic  basis  of 
classification  are  apparent  in  the  frequent  employment  of  combined 
names  indicating  the  mental  uncertainty  of  the  pathologist,  as  sar- 
coma carcinomatodes,  or  carcinoma  sarcomatodes:  and  it  is  not  an 


370 


Tumors. 


uncommon  thing  for  good  histologists  to  make  use  of  different 
diagnostic  terms  to  describe  one  and  the  same  tumor,  one  perhaps 
calHng  it  sarcoma,  others  endothehoma,  perithelioma  or  alveolar 
sarcoma.  This  is  but  natural  when  one  considers  the  number  and 
variability  of  connective  tissue  tumors  and  their  combinations,  the 
differences  of  composition  which  exist  in  different  parts  of  one  indi- 
vidual growth  and  the  changes  and  metaplasias  which  are  possible, 
these  features  preventing  any  schematic  and  clearly  defined  classi- 
fication. 

The  macroscopic  appearances  of  sarcomata  are  naturally  very 
variable  on  account  of  the  many  types  of  histological  structure 
which  they  may  present.  Some  are  soft,  others  hard ;  their  color  is 
generally  a  grayish-white,  similar  to  the  tissue  of  lymph  glands  or 
foetal  brain  tissue  (hence  the  old  terms  medullary  sarcoma  and 
encephaloid  sarcoma).  They  are  usually  rapidly  growing  tumors, 
some  growing  in  nodular,  nodal  or  lobulated  forms,  others  as  infil- 
trative growths.  Their  expansion  not  only  occasions  considerable 
pressure  upon  the  surrounding  tissues  and  organs,  but  by  stretching 
the  tissues  they  approach  the  surface  of  the  organ,  break  through 
the  mucous  membrane  or  external  skin,  or  destroy  the  part  from 
which  they  arise  by  their  deeper  growth.  By  their  infiltrative 
growth  and  penetration  between  the  tissues  sarcomatous  formations 
occaeion  marked  enlargement  in  bulk  and  expansion  of  the  part 
aft'ected.  Isolated  tumors,  reaching  from  five  to  seventeen  kilograms 
in  weight,  and  enlargements  of  organs  of  perhaps  twice  or  three 
times  the  normal  size,  are  not  uncommon  in  sarcomatosis  of  the 
kidneys,  liver,  rectum,  spleen  and  lymph  glands.  The  great  tendency 
to  infiltration  occasions  daughter  nodes  in  the  vicinity  of  the  orig- 
inal growth  and  leads  to  metastases,  which  are  especially  likely  to 
follow  the  blood  current.  Penetration  into  blood  vessels  is  often 
apparent  to  the  unaided  eye  in  case  of  large  veins,  as  those  of  the 
liver.  The  tissue  increase,  both  in  the  orimarv  and  secondarv 
tumors,  is  always  due  to  the  independent  proliferation  of  the  sar- 
coma cells,  the  formation  of  blood  vessels  (associated  prolifera- 
tion), however,  proceeding  directly  from  the  organ  in  which  the 
sarcoma  cells  are  distributed,  apparently  from  a  peculiar  influ- 
ence exerted  by  the  tumor  cells  upon  the  endothelium  (Ribbert). 
These  vessels,  proliferating  in  association  with  the  tumor  cells,  for 
the  most  part  maintain  their  capillary  type,  often,  of  course,  as 
wide  endothelial  tubes ;  the  frequence  of  haemorrhage  in  the  sar- 
coma substance  being  due  to  the  thinness  of  their  walls.  Because 
of  this  abnormality  in  the  blood  supply,  which  may  not  keep  pace 


Sarcoma.  371 

with  the  rapid  exuberance  of  th?  celhilar  growth,  various  retro- 
grade metamorphoses  are  possible,  of  which  fatty  degeneration  is 
the  most  common. 

Nothing  certain  is  known  of  the  development  and  cause  of  origin 
of  sarcomata.  Now  and  again  sarcomata  and  their  combined 
growths  are  met  following  traumatism  (fractures  of  bone,  contu- 
sions and  injuries  to  the  soft  parts)  ;  from  the  analogy  shown  by  lux- 
uriant traumatic  granulation  tissue  growth  to  the  sarcomata,  it  may 
be  supposed  that  some  instances  are  due  to  lesions  causing  loss 
of  tissue  tension,  and  further  investigation  of  convincing  ex- 
amples would  be  of  much  interest  in  this  line.  In  the  second  place 
sarcomata  may  be  thought  of  as  perhaps  related  in  their  origin  with 
faults  of  development,  both  because  they  are  common  in  man  and 
animals  in  early  life  and  because  their  cellular  character  is  sugges- 
tive of  embryonal  conditions. 

The  principal  seats  of  primary  sarcoma  formation  in  animals 
are  the  bones  (jaw  in  dogs  and  horses,  cranial  cavity  in  cattle),  the 
lymphatic  glands  and  spleen  (dogs,  cattle),  and  the  intestine  (cat- 
tle)   (Frohner,  Leisering,  Dieckerhoff,  Siedamgrotzky,  Casper). 

[Of  the  sarcomas  it  may  be  said  in  a  general  way,  to  which  ex- 
ceptions are  not  infrequent,  that  the  spindle  cell  varieties  more 
commonly  arise  from  the  denser  types  of  connective  tissue  as  the 
periosteum,  fasci?e,  intermuscular  septa  and  capsules  or  framework 
of  organs ;  and  that  the  round  cell  forms  more  commonly  originate 
from  the  softer  and  more  cellular  types  of  connective  tissue,  as  the 
lymphoid  structures  and  the  intraparenchymatous  intercellular  con- 
nective tissue  of  organs.  The  giant  cell  sarcoma  is  practically  lim- 
ited to  the  bone  marrow,  usually  growing  toward  the  ends  of  the 
shafts  of  the  long  bones. 

In  the  same  comprehensive  way,  again  with  many  exceptions,  it 
may  be  expected  that  the  round  cell  types  are  the  larger,  more  irreg- 
ular and  more  infiltrative  as  primary  growths,  and  of  a  soft  fleshy 
consistence,  highly  vascular,  and,  before  the  blood  has  been  washed 
out,  of  a  red,  translucent,  soft  fleshy  appearance  (paler,  as  above  de- 
scribed, after  the  blood  has  been  removed  or  if  the  growth  when 
obfained  from  the  subject  is  relatively  freed  from  its  blood  con- 
tents) ;  the  spindle  cell  form  tending  in  the  same  general  and  un- 
fixed manner  to  be  smaller  in  size,  less  infiltrative,  but  rarely  encap- 
sulated, more  regular  in  outline  and  nodular  or  lobulated,  somewhat 
firmer  in  consistence  and  of  a  lighter  color  than  the  round  cell  varie- 
ties. The  giant  cell  sarcoma  usually  causes  an  expansion  of  the 
bone  shaft,  is  covered  with  a  thin  and  generally  imperfect  shell  of 


372  Tumors. 

bone,  the  interior  sarcomatous  mass  soft  (sometimes  almost  mushy), 
deep  red  and  hgemorrhagic  and  bleeding  freely  when  cut  into.  The 
hsemorrhagic  tendency  is  often  so  pronounced  that  the  term  aneu- 
rismal  sarcoma  has  been  applied  to  describe  this  feature  of  marked 
vascularity. 

Of  the  sarcomata  above  described  by  the  author,  the  highest 
grade  of  malignancy  from  metastasis  is  met  among  the  round  cell 
varieties,  especially  the  small  round  cell  sarcoma  and  the  alveolar 
round  cell  sarcoma  ;  spindle  cell  sarcomata  are  also  decidedly  metas- 
tatic in  the  small  cell  form ;  the  large  spindle  cell  sarcoma  being 
sometimes  metastatic,  but  especially  showing  its  power  in  this  direc- 
tion by  recurrence  after  removal  (hence  sometimes  called  recurrent 
fibroid  tumor).  The  giant  cell  sarcoma  is  often  said  not  to  give" 
rise  to  metastasis ;  but  this  not  strictly  the  case,  as  in  man  the  editor 
has  encountered  two  well-established  instances  of  metastatic  for- 
mations of  this  type,  once  from  a  myeloid  sarcoma  of  the  upper  end 
of  the  tibia  to  one  of  the  tarsal  bones,  and  again  from  a  similar 
growth  in  the  upper  end  of  the  shaft  of  the  femur  to  the  pelvis]. 

Lymphomata. 

By  the  names  lyinphoniata  or  lyinpho-sarcomata  are  meant  pro- 
gressive proliferations  of  a  tissue  of  the  type  of  that  of  the  lym- 
phatic glands,  originating  from  the  lymphatic  structures  of  the 
body.  Lymphatic  tissue  is  found  in  the  lymph  glands,  bone  marrow, 
spleen  and  thymus  gland  and  is  represented,  too,  by  microscopically 
small  developmental  areas  of  lymphocytes  widely  distributed 
through  the  connective  tissue  of  the  system.     The  number  and  size 

On 

of  these  depots  and  developmental  foci  of  the  leucocytes  and 
lymphocytes  vary  considerably  in  dififerent  individuals,  even  physio- 
logicallv.  For  example,  the  thymus  gland  is  often  found  double  the 
size  attributed  to  it  as  normal,  and  in  some  calves  the  intestinal 
lymphatic  glands  are  so  much  enlarged  and  so  confluent  that  the 
mucous  membrane  in  its  entire  extent  may  approach  a  centimeter 
in  thickness,  without  the  possibility  of  speaking  of  this  '^o-called 
lymphatismus  [status  lyiuphaticus]  directly  as  a  pathological 
condition  (Johne).  So,  too,  in  calves  and  also  in  goats,  hogs  and 
dogs,  enlargements  of  the  lymph  glands  are  found  which  are  due  to 
proliferation  of  their  lymphoid  tissue,  and  from  one  standpoint  may 
be  regarded  as  hyperplasias,  but  which  assume  the  character  of 
tumors  in  their  progressive  infiltrative  extension  and  are  very 
dpvibtfyl  so  far  as  the  history  of  their  causation  is  concerned.    These 


Lymphoma. 


373 


growths  are  spoken  of  as  lymphomatosis,  progressive  lymphomata, 
Hodgk ill's  Disease  or  malignant  lymphosareomatosis.  The  afifec- 
tion  manifests  itself  by  a  gradual  enlargement  of  one  group  of 
lymph  glands  in  excess  of  the  rest.  In  all  parts  where  the  glands 
are  palpable,  as  in  the  flexures  of  joints,  in  front  and  back  of  joints, 
along  the  neck,  in  the  throat,  they  may  be  recognized  as  rounded 


^,^/l^r^'. 


Fig.  105. 
Urinary    bladder   of  cow   beset  witli   l.vmiibi.mara    (laid   open). 

oval  movable  bodies,  enlarged  to  the  size  of  a  nut  or  that  of  a  fist. 
At  autopsy  the  l}Tnph  glands  of  the  interior  of  the  body  are  also 
found  changed  into  large  nodulated  masses,  sometimes  reaching 
the  size  of  a  human  head.  At  first  the  capsules  of  the  glands  are 
retained  and.  as  a  consequence,  the  nodular  enlargements  are  well 
defined ;  their  consistence  varies,  sometimes  soft,  sometimes  firm, 
and  the  surface  of  section  has  throughout  a  uniform  grayish-white 


374 


Tumors. 


color.  The  minute  structure  of  these  enlarged  glands  corresponds 
more  or  less  closely  to  that  of  normal  ones,  but  differentiation  into 
follicles,  lymph  cords  and  lymph  sinuses  is  less  marked,  and  the  tis- 
sue is  more  uniform.  The  tumor  mass  is  made  up  of  a  finely  fibrillar 
or  more  coarsely  trabecular  network  of  connective  tissue  and  blood 
vessels  in  which  are  uniformly  distributed,  in  close  apposition  to 
each  other,  cells  of  the  type  of  lymphocytes.  In  addition  to  the 
small  rounded  lymphocytes  with  round  nuclei  rich  in  chromatin, 
there  may  be  found  larger  cells  like  those  often  met  as  early  or 
provisional  forms  in  the  germinal  centers  of  the  follicles,  and  once 
and  a  while  a  few  giant  cells  (Ribbert).  Besides  the  proper  lymph 
nodes  the  follicles  of  the  intestine,  pharnyx,  and  especially  the 
lymphatic  foci  of  the  spleen,  also  undergo  enlargement.     The  last- 


Fig.  106. 
Malignant  lymphoma  in  kidney  of  hog. 


named  organ  may  reach  very  marked  excess  of  volume,  either  show- 
ing its  Malpighian  bodies  increased  to  the  size  of  a  millet  seed  or 
a  pea  (follicular  hyperplasia  of  the  spleen),  or  the  whole  pulp  as 
well  evincing  great  increase  of  its  lymphatic  constituents  as  a 
grayish-red  swollen  mass  {diffuse  splenic  hyperplasia). 

In  the  course  of  the  progressive  proliferation  the  lymphatic 
tissue  passes  beyond  its  original  limits,  the  capsules  of  the  lymph 
nodes  are  broken  through  and  the  bunches  of  glands  coalesce  into 
shapeless  masses.  Diffuse. extension  takes  place,  the  adjacent  soft 
parts  becoming  occupied  by  the  penetrating  lymphoma,  and  an  infil- 
trative type  of  enlargement  is  assumed  from  which  the  glandular 
parenchymatous  structures,  like  the  liver  and  kidneys,  may  also 
become  diffusely  and  very  markedly  enlarged.  The  infiltrating 
lymphoid  tissue  gives  to  the  parenchyma  of  such  parts  a  pale  gray 


Lymphoma. 


375 


color,  which  may  be  either  diffuse  or  present  an  irregular  mottling. 
The  infiltration  follows  along  the  lymph  spaces  of  the  connective 
tissue,  especially  along  the  perivascular  lymph  channels,  and  may 
lead  by  special  local  accumulations  of  the  tumor  cells  to  the  pro- 
duction of  new  tumor-like  nodes  as  well.  The  lymphosarcomatous 
cells,  however,  also  penetrate  into  the  blood  vessels,  and  by  con- 


Fig.  Ill 


Multiple  lymphomata  in  liver  of  hog   (general  progressive  lumphomatosis). 

vection  may  occasion  metastatic  nodules  in  various  organs,  especially 
in  their  lymphatic  structures.  The  fact  that  the  lymph  glands  in 
order  of  position  undergo  enlargement  one  after  another,  and  that 
the  metastases  are  principally  located  in  the  lymphatic  structures, 
may,  it  is  thought,  be  due  to  chemotactic  influences  of  related 
type's  of  cells   (Ribbert).     It  may  be  that  the  lymphosarcoma  cells 


Z7^ 


Tumors. 


are  lodged  in  the  lymph  centres  having  passed  through  the  capil- 
laries, because  the  lymph  cells  present  in  these  foci  have  an  attrac- 
tion for  them ;  besides,  apart  from  such  a  mode,  the  tumor  cells 
carried  in  the  lymph  stream  are  bound  to  enter  the  lymph  glands, 
where  they  are  filtered  from  the  lymph  and  remain.  According  to 
Ribbert's  views,  progressive  lymphomatosis  is  a  true  tumor  forma- 
tion. The  successively  involved  glands  show  the  inception  of  the 
new  formation  often  by  well  defined  foci,  sometimes  only  to  be 
recognized  in  the  peripheral  sinus  of  the  node,  this    arguing    for 


I-ympliosarconat(isis  of  liver  of  cow    (low  power). 
Fig.  108. 


transference  of  the  tumor  element  from  a  primary  focus.  By  others 
it  is  believed  that  some  infectious  process,  bacterial  in  nature,  is 
connected,  and  that  the  microorganisms  gain  access  to  the  lymph 
glands  in  the  lymph  circulation  and  set  up  proliferative  processes 
in  the  nodes ;  but  as  yet  nioculation  expenments  have  given  no  posi- 
tive evidence.  [The  author's  statement  is  true;  yet  glandular  en- 
largements, clinically  regarded  as  belonging  to  Hodgkin's  disease, 
have  repeatedly  been  found  to  be  tuberculous  in  nature.  The 
lymphomatoses  probably  should  be  looked  upon  as  of  two  types,  one 


Melanoma.  t,J7 

of  which  is  best  regarded  as  merely  a  lymphatic  hyperplasia  occas- 
sioned  by  microorganisms  or  toxic  substances  which  are  in  some 
way  brought  to  the  lymph  nodes  (and  some  of  these  are  tuberculous, 
the  remainder  probably  being  products  of  a  variety  of  microbic  and 
toxic  influences).  The  second  group  may  be  properly  referred  to 
the  class  of  the  sarcomas  and  spoken  of  as  lymphosarcoma  and 
lymphadenoid  sarcoma.  The  term  lymphoma  may  be  provisionally 
retained  to  cover  the  group  of  uncertain  or  indistinguishable  exam- 
ples, but  has  no  other  place  properly  in  tumor  nomenclature.  If 
we  limit  ourselves  to  that  series  of  cases,  to  which,  from  their 
higher  infiltrative  and  metastatic  tendency  (especially  where  we  can 
recognize  that  the  secondary  nodules  are  true  metastases  and  not 
mere  hyperplasias  of  previously  existing  lymphoid  foci  which  may 
have  been  induced  by  an  original  microbic  or  toxic  cause),  the 
name  sarcoma  may  be  reasonably  applied.  It  should  be  added  that 
lymphosarcoma  is  a  highly  malignant  type  of  sarcoma,  ranking  with 
the  ordinary  small  round  cell  variety  in  the  severity  of  malignancy 
from  metastasis.  It  is.  of  course,  difficult  to  make  the  separa- 
tion in  a  large  group  of  cases,  but  as  far  as  possible  we  should 
endeavor  to  exclude  from  the  term  lymphosarcoma  tliose  cases  in 
which  enlargements  manifest  any  appearances  of  infectious  origin. 
Where  among  these  there  is  evidence  of  tuberculosis  of  course 
the  case  is  promptly  referred  to  as  tuberculous  lymphatic  hyper- 
plasia. For  the  rest  of  the  cases  the  non-distinctive  term  Hodg- 
kin's  disease  may  be  employed  if  desired ;  and  it  is  well  to  keep 
clearl}'  in  mind  that  the  affection  known  as  lymphatic  leub^emia, 
both  acute  and  chronic,  bears  close  relationship  with  the  latter 
group.] 

Melanomata. 

A  mclaiionia.  iiiclaiiosarcoiua  (cliroiiiatoplwroma),  or  pig- 
mented tumor,  is  characterized  by  a  black-brown  or  slate-gray 
color  produced  by  the  pigment  cells  (chromatophores)  which 
constitute  the  growth.  Normally  pigment  cells  are  found  as 
specially  difterentiated  connective  tissue  elements  in  the  skin 
and  choroid  coat  of  the  e_\e,  and  in  some  animals,  as  sheep,  also  in 
the  'pia  mater  of  the  brain.  The  melanomata  take  their  origin 
from  these  cells  and  are  therefore  found  most  frequently  in  the 
skin,  being  especially  common  in  horses.  It  is  peculiar  that  gray 
and  light  colored  horses,  which  as  foals  had  a  dark  coat  of  hair, 
should    be    especially   prone    to    these    tumors ;    and    it    may    be 


378 


Tumors. 


presumed  that  irregularities  of  their  loss  of  pigment  underlies 
the  anomaly.  Melanoma  may,  however,  also  occur  in  brown 
horses  and  has  been  seen  once  in  a  black  (Hall).  In  most 
instances  these  growths  develop  in  horses  in  the  region  of  the  root 
of  the  tail,  the  anus  and  external  genitalia.  In  these  positions 
they  form  nodes  which  protrude  like  boils  beneath  the  skin, 
attaining  the  size  of  several  fists  and  several  kilograms  in  weight. 
Secondary  nodes  are  formed  along  the  lymph  passages,  so  that 
in  the  cellular  tissue  of  the  pelvis  there  may  be  found  whole 
chains  of   tumor  nodes ;   and  by   infiltrative   growth  the   tumor 


Fig.  109. 
Section  through  horse's  tall  involved  by  melanoma. 

may  completely  invade  the  cutis  and  subcutaneous  tissue,  and 
cause  widespread  thickening  and  swelling.  The  growth  is 
usually  slow ;  it  may  continue  for  several  years  as  a  circum- 
scribed and  strictly  local  process,  at  other  times  being  highly 
metastatic  and  causing  an  extensive  generalized  melanosarco- 
matosis,  with  secondary  nodes  in  the  lung,  pleura,  spleen,  liver, 
kidneys,  bones,  musculature  and  elsewhere.  Melanomata  of  the 
same  nature  as  the  above  have  been  met  also  as  primary  growths 
in  the  cellular  tissue  near  the  parotid  gland,  in  the  pancreas 
(Kasewurm),  intestine  (Csokor),  at  the  base  of  the  heart  (Dex- 
ler),  and  in  the  spleen. 


* 


Melanoma. 


379 


In  cattle  melanomata  are  of  less  frequent  occurrence.  Metz 
saw  two  cases  in  white  animals ;  in  one  the  tumor  was  situated 
in  the  dewlap,  in  the  second  in  the  pelvic  cavity  near  the  uterus. 
Hamburger  found  one  tumor  of  this  kind  in  the  diaphragm ; 
Hoare  removed  a  melanoma  weighing  fifteen  kilograms  from  the 
temporal  region  of  a  brown  ox.  Bollinger  has  recorded  the 
occurrence  of  a  congenital  melanoma  of  the  size  of  a  fist  in  the 
cranial  cavity  of  a  thirty-day-old  calf;  Wulf,  a  similar  growtk 
in  the  subcutaneous  tissue  of  the  ankle  of  a  calf.  In  sheep 
Worseley  has  reported  a  case  of  melanosarcomatosis  involving 


~^^ 


r^-^-^-^. 


Fig.  110. 
Microscopic  section  of  sliin  of  horse  infiltrated  with  melanoma. 

the  lumbar  region,  mammary  glands,  lungs  and  liver.  In  the  dog 
the  author  has  observed  a  melanoma,  springing  from  the  gums, 
and  Bruckmiiller  one  at  the  base  of  the  brain. 

Some  melanomata  have  a  firm,  rather  dry  appearance ;  others 
are  found  of  soft  consistence.  The  cut  surface  is  uniformly 
dark,  or  sepia-brown  or  slaty ;  when  handled  the  fingers  are 
soiled  as  if  with  shoe-blacking. 

Microscopically  the  pigment  is  found  in  the  form  of  brown- 
ish black  granules,  which  are  distributed  in  the  fluids  of  the 


380  Tumors.  . 

tumor  and  within  the  cells.  The  latter  elements  are  seen  as 
variably  shaped,  irregularly  rounded,  fusiform  and  branched 
cells,  their  cytoplasm  usually  so  thickly  loaded  with  the  dark 
brown  granules  that  the  nucleus  is  obscured ;  at  places,  however, 
they  may  be  found  entirely  free  from  pigment.  The  cells  are 
usually  so  closely  packed  together  that  their  outlines  cannot 
always  be  dififerentiated.  The  tumor  tissue  is  very  clearly 
defined  from  the  rest  of  the  tissues,  into  the  lymph  spaces  of 
which  the  neoplasm  can  be  seen  to  be  extending  its  way,  afford- 
ing an  excellent  demonstration  under  the  microscope  of  the 
mode  of  propagation  of  these  growths.  The  cells  are  so  easily 
loosened  in  the  softer  specimens  that  the  tumor  mass  may  stand 
out  like  thick  pultaceous  material ;  Csokor  has  observed  in  the 
case  of  a  horse  with  the  intestinal  mucous  membrane  (colon) 
the  seat  of  melanoma,  the  discharge  of  black  fecal  matter ;  and 
Bollinger,  Bruckmiiller  and  Semmer  have  found  the  pigment 
gramdes  in  the  blood  (melan:cmia). 

The  pigment  material  known  as  melanin,  certainly  does  not 
come  from  the  blood  (iron  free),  but  is  formed  by  a  specific 
activity  of  the  chromatophorous  cells,  as  Berdez  and  Nencki 
have  shown  ;  the  important  proportion  of  sulphur  in  its  compo- 
sition suggests  that  it  is  a  derivative  of  albuminous  bodies. 

The  orisfin  of  melanomata  is  necessarilv  in  some  wav  related 
to  developmental  disturbances  which  give  rise  to  excessive  pro- 
duction or  misplacement  of  pigment  cells;  their  occurrence  as 
congenital  tumors  and  the  fact  that  in  man  the  growths  are 
known  to  frequently  take  their  start  from  congenital  pigment 
moles  of  the  skin,  are  evidence  in  favor  of  such  a  view. 

The  malignancy  of  these  growths  is  not  uniform;  as  above 
stated,  some  may  remain  in  their  primary  situation  for  years 
without  appreciable  enlargement,  and  may  not  recur  when  re- 
moved, but  others,  especially  the  softer  forms,  spread  rapidly  and 
widely  and  give  rise  to  great  numbers  of  secondary  nodes.  [The 
melanotic  sarcoma  of  man.  most  commonly  met  in  the  eye,  is  ex- 
tremely malignant,  ranking  probably  first  of  all  in  the  list  of  sar- 
comata in  this  respect.] 

Endotheliomata,    Peritheliomata,    Cholesteatomata. 

By  the  term  endothelioma  is  meant  a  tumor  which  is  com- 
posed of  endothelial  cells  of  connective  tissue  derivation,  espe- 
cially those  of  blood  vessels  and  lymph  vessels,  as  well  as  those 


Endothelioma.  381 

of  the  dura  mater  of  the  brain  and  spinal  cord.  EndotheHomata 
in  their  structure  stand  relatively  midway  between  the  atypical 
connective  tissue  growths  and  epithelial  tumors,  and  resemble  now 
one  and  now  the  other  of  these  so  closel}-  as  to  make  their  distinc- 
tion from  sarcomata  or  carcinomata  often  practically  impossible 
where  only  single  bits  of  die  growths  are  subjected  to  micro- 
scopic examination.  They  dilTer  from  cancers  in  the  history  of 
their  development,  the  latter  taking  their  origin  from  epithelium, 


v  if        '•    •      '      ''  '     "  c  f-  .f     5^ 

_        _    ". ,  _      ^.      Jt,  «»,    -K.  ^t 


Fig.   111. 


Endothelioma  of  lymphgland  (human):  a,  lymphoid  tissue  of  gland;  h,  leucocytes 
in  nearly  obliterated  lymph-sinus  ;  c,  endotlielial  cells  proliferated  from  lining 
of   lymph-sinus. 

either  ectodermal  or  entodermal,  while  the  true  endotheliomata 
are  of  mesoblastic  origin.  It  is  more  difficult  to  define  them 
from  sarcomata,  the  cells  of  the  latter  being  also  derived  from  the 
middle  germinal  layer ;  and  for  this  reason  some  authors  speak 
of  them  as  endothelial  sarcomata.  (The  layer  of  so-called  endo- 
thelial cells  lining  the  large  serous  cavities  of  the  body,  the  coelo- 
matous  lining,  is  to  be  regarded- as  epithelial  and  the  tumors 
which  arise  from  these  cells  are  therefore  to  be  classed  as 
cancers.) 


382  Tumors. 

The  cells  of  an  endothelionia  present  the  same  polygonal, 
flattened,  fusiform  and  polyhedral  forms  as  the  fibroblasts  and 
angioblasts,  the  cells  of  the  blood  and  lymph  vessels  being,  in 
fact,  formed  originally  of  the  same  material.  In  the  tumors  they 
are  arranged  as  scales,  or  in  cylindrical  cords  or  in  hollow  tubu- 
lar manner  so  as  to  form  a  network  with  thickened  nodal  points, 
and  are  supported  by  a  vascular  stroma.  The  microscopic  appear- 
ance is  therefore  very  like  that  of  an  alveolar  sarcoma  or  carci- 
noma; sometimes  the  arrangement  of  the  cells  in  lamellae  may  be 
concentric  like  the  tunic  of  an  onion. 

Those  endotheliomata  which  take  their  origin  from  the  outer 
coat  (adventitia)  of  the  bloodvessels  (from  the  perithelial  cells) 
and  are  recognized  as  forming  mantles  of  tumor  cells  about  the 
blood  vessel  and  its  branches,  are  generally  spoken  of  as  pcri- 
theliomata. 

Retrograde  changes  which  occur  in  endotheliomata  may  give 
an  unusual  appearance  to  some  forms,  in  consequence  of  which 
special  names  are  applied.  As  an  example  the  cylindrical  cords 
may  undergo,  hyaline  degeneration  of  their  endothelial  cells,  be 
transformed  into  shining  homogeneous  structures,  standing  out 
conspicuously  in  transverse  section  like  hyaline,  concentrically 
laminated  balls  or  masses ;  this  appearance  has  led  to  their  being 
called  cylindroniata.  In  other  instances  calcareous  deposits  (in 
the  form  of  globules,  needles  and  club-shaped  masses)  occur  in 
the  structure  of  the  growth,  giving  a  grittiness  to  the  tumor  in 
section  and  making  the  cut  surface  rough  and  sandy ;  these  are 
especially  met  in  the  brain  and  are  known  as  psammomata  {acer- 
vuloma,  sand  tumor).  The  endotheliomata  which  -develop  from 
the  choroid  plexus  of  the  brain  are  always  richly  infiltrated  with 
cholesterin  deposits,  and  are  called  in  a  superficial  way  choles- 
teatomata. 

However  these  changes  or  depositions  which  give  occasion  for  the  special 
names  indicated  are  not  absolutely  restricted  to  one  particular  type  of  tumor. 
In  the  collection  of  lime  and  cholesterin  it  must  be  kept  in  mind  that  the 
cells  of  the  neoplasm  are  preserving  qualities  of  the  cells  from  which  they 
had  their  derivation,  for  brain  sand  and  cholesterin  are  found  normally  also 
in  the  pineal  gland  and  in  the  choroid  tissue.  True  epithelial  tumors,  how- 
ever, which  occur  in  the  cranial  cavity  and  are  referable  to  inclusions  of 
epidermoidal  rests  usually  contain  cholesterin,  and  it  is  also  met  in  dermoid 
cysts  or  epidermoid  cysts  of  the  subcutaneous  tissue;  these  types  requiring 
the  acceptance  of  a  further   class,  the  epithelial   cholesteatomata. 

Contributions  recording  the'  occurrence  of  endotheliomata  in 
animals  are  very  meagrely  found  in  literature.    Dexler  met  in  a 


Cholesteatoma;  Papilloma.  383 

dog-  an  endothelioma  originating  from  the  spinal  dura  mater; 
Kijnnemann  a  psammoma  of  the  cranial  dura  mater  about  the 
size  of  a  duck's  egg,  overlying  the  anterior  part  of  the  brain  in 
a  cow.  Cholesteatomata  have  been  found  rather  frequently  in 
the  lateral  ventricles  in  the  horse ;  met  in  this  location  they  are 
rounded,  reniform  nodes,  varying  in  size  from  that  of  a  lentil  to 
that  of  an  egg,  usually  occurring  bilaterally,  a  tumor  suspended 
from  the  choroid  plexus  in  each  ventricle.  The  surface  is  smooth 
and  shining,  sometimes  granular;  the  color  white,  gray  or  grayish- 
yellow;  the  consistence  about  that  of  the  liver,  the  cut  surface 
slightly  gritty  and  the  cholesterin  recognizable  in  tiny  opalescent, 
shiny  spots.  Microscopically  these  tumors  are  made  up  of  blood- 
vessels, a  loose  connective  tissue  stroma  and  the  endothelial  ele- 
ments, which  have  grown  from  the  bloodvessel  wall ;  between 
these  cells,  in  the  vessel  walls  and  in  the  widened  lumina  of  the 
latter  the  cholesterin  may  be  seen  in  the  form  of  superimposed, 
step-like  plates  with  the  borders  broken  out.  In  addition  round 
cells  and  pigmentary  deposits  may  also  be  found.  (Cornil  and 
Ranvier  speak  of  the  tumors  in  question  as  angiolithic  sarco- 
mata; Casper  employs  the  term  hsemangiosarcoma  perivascu- 
losum). 

[The  position  taken  by  the  author  in  excluding  from  the 
endotheliomata  tumors  originating  from  endothelium  of  the 
large  serous  sacs,  is  not  generally  accepted ;  and  endotheliomata 
of  the   pleura   especially   have   been    frequently   described. 

Endotheliomata  as  a  rule  are  slowly  growing  tumors  and 
although  capable  of  metastasis  are  generally  not  marked  by 
many  secondary  formations.  This,  however,  'in  some  individual 
examples  is  quite  reversed  and  high  metastatic  malignancy  is 
manifested.  So,  too,  in  most  cases  they  are  not  recurrent  after 
extirpation,  but  here  again  exceptions  must  be  recognized. 
They  may  occur  as  multiple  primary  growths.  The  subdivisions 
above  mentioned,  cylindroma,  cholesteatoma  and  psammoma. 
are  as  a  rule  merely  local  growths,  and  arc  among  the  least 
metastatic  forms  of  endotheliomata.] 

Papillomata. 

The  name  papilloma  is  applied  as  a  comprehensive,  even  if 
not  well  chosen,  term  for  fibroepithelial  neoplasms  which  occur 
on  the  surface  of  the  skin  and  mucous  membranes  in  the  form 
of  warty,  conical,  coralline,  villous  or  nodular  proliferations  of 


384 


Tumors. 


the  papilla  and  their  overlying  epithehum.  The  physiological 
prototype  of  this  combination  of  tissue  and  its  source  of  develop- 
ment are  in  fact  the  epithelial-covered  papillae  of  the  skin,  but 
in  their  pathological  proliferation  the  quantitive  relations  be- 
tween the  two  forms  of  tissue  are  very  irregular.  In  some 
tumors  the  connective  tissue  growth  is  so  predominant  that  the 
tumor  practically  consists  of  thick  clumps  of  this  tissue  covered 
only^  by  a  thin  layer  of  epithelium  rather  stretched  over  the  mass 


Fig.   112. 
Cutaneous  papillomatosis  of  beef. 

than  growing  with  it  (for  which  reason  some  authors  prefer  to 
speak  of  such  a  specimen  as  fibroma  papillare),  the  superficial 
papillary  structure  being  only  recognizable  under  the  micro- 
scope. In  other  instances  the  fibrous  tissue  of  the  base  of  the 
tumor  sends  out  long  branched  villous  processes,  or  may  undergo 
changes  which  give  it  a  soft,  oedematous  or  very  vascular  appear- 
ance ;  and  again  the  keratous  epithelium  may  form  so  thick  a 
laver  as  to  throw  the  connective  tissue  substructure  into  insig- 
nificance. Different  types  of  these  iibroepithelial  autoblastomata 
may  be  distinguished  by  taking  such  features  into  consideration. 


Papilloma. 


385 


On  the  skin  and  nmcons  membranes  covered  with  <;quamons 
epithelium  they  occur  as  rounded  projections,  sometimes  only 
as  large  as  a  pea  or  nut  (zvarts,  z'crniccc) ,  simple  local  hyper- 
plasias of  the  papillary  body  with  smooth  epidermal  covering;  or 
they  sometimes  occur  in  clumps,  like  grapes,  as  cauliflower 
tumors  of  the  size  of  a  tist  [  paj^illouia  tiibcrositiii,  polyposuin.  coral- 
IlforiJic),    with     superficial     subdivisions,      provided      with      l)road 


f 


^'- 


'1.^^ 


X  J 


if. 


y^-j 


< 


-\.;V 


'^'^^f; 


It.    3 


klfis  11  \ 


y  Jl  /  r   ^'^^^r^ 


Fig.  113. 
Section   (,f   papilloma   of  cow. 


peduncks  or  hanging  suspended  by  a  thin  stretched-out  pedicle ; 
or  again  as  thread-like  or  bristle-like  projections  (pa/^iUonia  fiU- 
forme). 

Under  the  microscope,  varying  with  these  external  shapes 
of  the  growth,  the  connective  tissue,  wdiich  is  made  up  merely 
of  spindle  cells  and  fibrils  with  bloodvessels,  may  be  seen  as 
papillae  of  varying  length  and  thickness  and  of  all  sorts  of 
shapes,  with  knotted  and  clubbed  branches  and  secondary  point- 
ed projections;  and  the  epiderm  in  a  single*  or  multiple  layer 
extends  over  this,   following  the  depressions  and   clefts,   in  which 


386 


Tumors. 


the  epithelium  may  become  keratosed  and  formed  into  concen- 
trically laminated  arrang^ements   (horny  pearls). 

Sometimes  these  papillomata  occur  congenitally    (two  cases 
of  the  kind  in  question  fully  described  by  Pirl  and  Trolldenier* 


v>  % 


^*.5 


Fig.    114. 

Papilloma  coralliforme  in  gullet  of  cow.  (T"he  oesophagus  has  been  everted  and 
the  mucous  surface  exposed  ;  the  partly  smooth  appearance  is  due  to  the  fact 
that  a  piece  of  wood  has  been  forced  into  the  lumen  of  the  tube  turned  in- 
side out.)      (Photograph.) 

in     foals),    probably    due    to     traumatic     intrauterine     lesions     of 
the  skin  caused  by  amniotic  threads.     By  some  authors  an  inf^c- 

*  Monatshep  f,  p,   TierJieilk,  1903. 


I\ipiili)iiia. 


387 


tious  cause  is  suspected  for  ccM-tain  forms  of  papillomata  because 
the  affection  often  appears  in  a  number  of  animals  at  the  same 
time  in  one  stalile  in  wide  distribution  over  the  cutaneous  sur- 
face; development  after  chronic  .intiammatory  irritation  of  tlie 
skin  has  also  been  observed.  Especiall}-  in  the  skin  of  the  udder 
of  the  cow  and  in  young-  cattle,  but  also  in  other  positions  in  this 
species  there  often  develop  g-reat  numbers  of  w^arty  and  nodular 
papillomata  which  ma\-  weigh  en  jiuissc  many  pounds.  These 
superficially  divided  growths,  which  are  of  course  exposed  to 
traumatic  influences  and  contamination 
witli  foul  pus,  are  apt  to  become  mal- 
odorous from  maceration  of  the  desqua- 
mated epiderm  retained  in  the  depres- 
sions ;  they  often  become  oedematous 
and  swollen,  and  may  become  more  or 
less  suppurative  and  putrefactive  from 
the  influence  of  microorganisms,  which 
may  have  gained  access  into  these 
parts.  In  similar  manner  the  jiapillo- 
mata  frequently  developing  in  the  frog 
of  the  horse's  hoof  (known  as  hoof 
cancer  or  frog  cancer)  are  apt  to  break 
down  into  a  foul-smelling  mass  because 
of  incomplete  keratinization  of  the 
epithelial  surface  layer  and  contact  with 
all  sorts  of  germs  and  putrid  material 
(dung,   foul  pus). 

A  favorite  location  for  these  tumors 
is  the  oesophagus  of  cattle,  where  the 
papillfe  project  into  the  lumen  of  the 
tube  either  as  thorn-like,  bristle-like  or 
brush-like  prominences,  or  as  circumscribed  villous  or  coralline 
growths,  or  as  firm  nodular  bunches ;  the  passage  of  food,  es- 
pecially the  return  of  the  cud  (in  ruminants)  being  more  or 
less  interfered  with.  Papillomata  often  occur  also  in  the  psalter 
of  cattle  as  berry-like,  slightly  cedematous,  swollen-looking 
growths,  ranging  in  size  from  the  millet  seed  size  normal  to  the 
papillae  of  the  part,  to  pendant  rosette-like  bunches  of  projections 
half  the  length  of  the  finger,  clul)-shapefl  and  covered  smooth.ly 
with  epithelium.  In  dogs  the  lips,  buccal  cavity,  foreskin  and 
anus  are  the  principal  sites  of  papillomata. 


Fig.   ll.">. 

Congenital  papillnma  (if  pinna 
of  colt.  I  After  Troll- 
denier.) 


388  Tumors. 

In  the  urinary  and  gall  bladders  of  cattle,  in  the  former  also 
of  horses,  dogs  and  swine,  papillary  mucous  membrane  prolifera- 
tions occur,  usually  projecting  as  long  villous,  highly  branched 
growths  with  a  common  pedicle  into  the  cavity  of  the  viscus.  like 
the  tentacles  of  a  polyp  {papilloma  polyposum)  ;  they  are  usually 
very  soft,  succulent,  their  connective  tissue  oedematous  and  per- 
haps actually  myxomatous  (papilloma  polyposum  myxo'matodcs), 
or  in  other  cases  the  seat  of  a  cellular  infiltration  and  presenting 
evidence  of  inflammatory  involvement.  Inflammatory  changes 
in  the  last  named  situations  are  so  frequently  accompanied  by 
mucous  membrane  proliferations  that  some  causal  relationship 
may  be  assumed  and  the  hyperplasia  of  the  mucous  membrane 
regarded  as  a  sequel  to  a  productive  inflammation   (Zellhuber). 

Where  the  epithelium  of  the  papillary  growth  of  the  skin  is 
not  desquamated  in  scales,  but  in  its  active  proliferation  forms 
thicker  and  thicker  horny  layers,  there  is  produced  a  hard  body 
which  continually  grows  more  and  more  prominent  and  acquires 
the  form  of  a  horn-like  outgrowth,  a  cutaneous  horn  (coniii  cuta- 
neiim).  These  structures  are  very  frequently  seen  in  cattle, 
especiallv  in  range  cattle,  occasionally  attaining  a  length  of  half 
a  meter,  growing  from  the  forehead  or  neck,  or  as  a  short 
conical  horn  from  the  skin  of  the  udder.  Now  and  then  large 
spirally  curved  cutaneous  horns  are  seen  in  goats  in  the  thoracic 
and  abdominal  walls;  in  sheep  in  the  car  and  back;  in  horses  and 
dogs  as  small  claw-like  horns  in  the  car  and  in  other  parts  of  the 
body.  (For  fuller  description  see  Casper,  Pathol,  d.  Gcschzviilste 
b.  Ticrcn.  Wiesbaden,  1899;  Kitt,  Spcz.  pathol.  Anatomic.  II.  Aufl., 
Stuttgart,  1901.) 

Papillomata  and  cutaneous  horns  are  regarded  as  benign,  non- 
recurrent, persistently  local  new  growths ;  they  manifest  an  unfavor- 
able tendency  only  from  their  size  and  situation. 

*  Adenoma. 

An  adenoma,  or  [epithelial]  glandular  tumor,  is  a  prolif- 
eration of  glandular  tissue,  with  reproduction  of  its  structural 
type,  in  the  forni  of  a  tumor.  Epithelium  and  a  vascular  con- 
nective tissue  stroma  in  definite  structural  relations  constitute 
glands,  and  the  two  forms  of  tissue  in  common  contribute  to  the 
formation  of  the  adenoma.  Whedier  the  epithelium  was  the 
primary  proliferating  element  and,  as  Borst  believes,  the  con- 
nective   tissue    cells    took    a    relatively    secondary    part    because 


Adenoma. 


3% 


of  their  tactile  sensibility,  is  an  open- question.  In  some  adeno- 
mata the  reverse  is  apparently  the  case,  the  connective  tissue 
proliferation  apparently  being-  the  major  feature,  in  its  prolifera- 
tion causing-  expansion  of  the  surfaces  of  the  gland  lumina  and 
thus  ali'ording  space  for  the  epithelial  gland  lining  to  develop. 
Both  tissues  proliferate  side  by  side  in  mutual  interdependence 
in  the  production  of  gland  tissue. 

There  are  as  many  varieties  of  adenoma  as  there  are  different 
glands  in  the  animal  body,  and  as  the  tumor  invariably  takes  its 
origin  from  a  gland  it  always  represents  a  histological  copy  of 
the  particular  gland  in  question.  The  growth  has,  too,  in  all 
instances  the  same  type  of  epithelium  which  characterized  the 
original  gland,  and  the   same  kind  of  connective  tissue   stroma  is 


f^ig    IIG. 

Adenoma,  of  size  of  human  head,  of  the  gall  ducts  iu  the  liver  of  cow  ; 

(cut   surface). 


preserved  in  more  or  less  precise  simulation  of  the  structure 
peculiar  to  the  parent  gland.  Corresponding  to  the  dififerent 
glands  these  tumors  may  be  divided  into  major  types  of  tiihular, 
alveolar  and  follicular  adenomata;  and  depending  upon  their 
origin  it  is  customary  to  speak  of  them  as  sweat-gland,  seba- 
ceous, hepatic,  salivary,  .renal  and  other  adenomata. 

In  this  pathological  proliferation  of  the  glandular  tissue  there 
occur,  how^ever,  manifold  modifications  and  abnormal  features. 
The  epithelium,  although  generally  exhibiting  the  same  structure 
and  even  secretory  function  as  the  original  type,  is  often  increased 


390 


Tumors. 


in  size  or  may  be  present  in  a  greater  number  of  layers,  and  its 
secretion  may  be  of  a  degenerative  character  (for  example,  from 
the  assumption  of  mucoid  change  by  the  adenomatous  cells  or 
their  destruction  by  excessive  fat  production).  The  connective 
tissue,  which  in  direct  limiting  relations  to  the  epithelium  forms 
its  tunica  propria  and  in  lobulated  types  of  gland  tissue  forms  a 
meshwork  of  septa,  is  often  developed  in  special  excess,  forming 
denseh'  fibrous  sclerotic  trabecula  which  embrace  the  glandu- 
lar ducts  in  compact  circular  investing  bands  {adenofibronia 
pcricanalicularc)  or  form  club-shaped  or  finger-like  projections, 
stretching  the  adenomatous  lumina,  increasing  the  surface  of 
the  glandular  canals  and  extending  into  the  latter  as  villous 
papillae    (adcuofibroiita  iiitracanaliciilarc,  adciiojiia  papUUfcnim). 


/ 


/ 


W 


Fig.  117. 

Adenoma  flavnm  of  liver  of  cow. 


The  tubular  or  vesicular  spaces  of  the  adenoma,  by  continu- 
ous and  progressive  formation  of  hollow  buds  lined  with  epi- 
thelium, become  more  and  more  branched  and  more  irregular  than 
in  the  normal  gland;  and  by  this  intricate  projection  of  epithelial- 
covered  connective  tissue  processes  into  their  interior  become 
changed  into  tortuous  passages  and  openings,  which  may  become 
quite  large.  The  cut  surface  of  an  adenoma  ma}^  in  this  way 
come  to  closely  resemble  a  section  through  a  head  of  cabbage, 
in  which  spaces  are  to  be  seen  between  the  layers  of  leaves.  As 
these  adenomata  are  completely  isolated  new  grow^ths  and  their 


Adenoma.  391 

canalicular  systems  are  in  no  way  in  communication  with  the 
emerging  ducts  of  the  noniuil  t^huuls,  an  accumulation  of  secre- 
tory material  and  desquamated  epithelial  cells  is  likely  to  be 
retained  in  their  passages  and  spaces :  thus  in  an  adenoma  of 
the  mammary  gland  milk  is  found  as  a  pathological  product ;  in 
follicular  adenomata  of  the  thyroid,  masses  of  colloid  matter;  in 
adenomata  of  mucous  glands,  mucin.  As  a  result  of  the  reten- 
tion of  such  material  the  walls  of  the  canals  and  alveoli  become 
stretched,  and  this  feature,  together  with  continuous  enlargement 
of  their  surfaces  from  increase  of  the  epithelial  lining  and  the 
connective  tissue  framework,  may  make  the  distended  cavities 
visible  to  the  naked  eye.  To  tumors  thus  altered  and  containing 
cavities  filled  with  fluid  the  term  cysfadc)io}na  is  applied ;  and 
where  villous  projections  of  the  lining  membranes  extend  into 
the  cavities  the  growth  is  known  as  cystadcnonia  papilliferum 
phylloidcs. 

The  growing  vascular  connective  tissue  of  the  adenomatous 
structure  is  sometimes  the  seat  of  haemorrhagic  effusions  or 
oedematous  swelling,  due  to  passive  congestion  and  transudation 
caused  by  kinking  of  the  folds  and  villi  projecting  into  the 
cysts.  Other  regressive  changes,  as  fatty  degeneration  or  coagu- 
lation necrosis,  may  also  be  observed.  In  some  instances  the 
stroma  of  the  tumor  is  a  tissue  very  rich  in  cells  and  of  a 
reticular  structure  resembling  a  sarcoma  or  myxoma  (adenosarcoma, 
adeiioinyxoma,   adenoma   sarcomatodes,    my.vomatodes) . 

Finally  glandular  tumors,  which  in  typical  cases  are  usually 
distinctly  limited  from  the  organ  in  which  they  are  situated, 
may  become  atypical  and  send  out  infiltrating  processes  into  the 
surrounding  tissue,  penetrating  into  the  lymph  vessels  and 
bloodvessels  and  thus  assume  the  character  of  a  malignant  fibro- 
epithelial  growth.  These  forms  are  known  by  the  names  adenoma 
destruens,  adenoearcinoma   [)nalignaut  adenoma]. 

Two  points  may  be  considered  in  attemptmg  an  explanation 
of  the  setiology  of  adenomata.  The  definitely  circumscribed 
nodular  adenomata  w'hich  develop  in  or  close  to  parenchymatous 
organs  are  doubtless  of  foetal  origin,  coming  from  misplaced, 
independently  developing  parts  of  a  gland.  Those  growing  as 
single  or  multiple  tumors  from  mucous  surfaces,  sometimes 
occupving  extensive  areas  of  the  mucous  membrane,  often  show 
in  themselves,  just  as  the  neighboring  parts  of  the  membrane 
mav  also  show,  evidences  of  chronic  inflammatory  change,  recog- 
nizable bv  cellular  infiltration  and  by  giving  rise  to  a  mixed  secre- 


392 


Tumors. 


tory  and  exudative  type  of  product.  These  peculiarities  as  well 
as  the  clinical  course  of  such  cases,  suggestive  of  their  origin  as 
direct  sequences  of  chronic  inflammatory  processes,  force  the 
conclusion  that  injuries  capable  of  causing  inflammation  may 
either  directly  or  indirectly  (disturbance  of  tissue  tension)  give 
origin  to  adenoma  production.  Mucous  membrane  and  glandu- 
lar vegetations  of  this  type  are  usually  spoken  of  as  glandular 
Iiypcrf>lasias  or  mucous  membrane  polyps.  It  should  be  recog- 
nized, however,  that  such  superficially  situated  adenomata  may 
become  inflamed  secondarily,  from  their  coming  in  contact  with 
irritants. 

The  most  frequent  type  of  adenomata  occurring  in  animals 
are  those  of  the  sebaceous  and  sweat  glands  {adenoma  seba- 
ceum, sudoriparuni)  in  the  skin  of  the  dog;  among  them  particu- 
larly growths  originating  from  the  perianal  glands,  presenting 
rounded,  nodular  and  lobulated  forms,  of  a  reddish  yellow  or  light 
yellow  color  and  giving  oft*  a  fatty,  greasy  fluid  (a  number  of 
descriptions  of  Siedamgrotzky,  Lienaux.  Werner).  True  ade- 
nomata of  the  liver  are  also  comparatively  common  in  cattle  and 
sheep  (Bollinger.  [Martin.  Siedamgrotzky.  Johne.  personal  obser- 
vations) as  sharply  defined  tumors,  surrounded  by  a  connective 
tissue  capsule,  situated  in  the  midst  of  the  hepatic  tissue.  These 
may  sometimes  be  found  as  large  as  a  human  head,  composed 
of  liver  cells  and  delicate  cob-web  like  connective  tissue  septa. 
They  are  usually  very  striking  because  of  their  bile-stained  yel- 
low to  green  hue.  Similar  to  these  there  also  occur  in  the  liver 
gall-duct  tumors,  with  dense  fibrous  stroma,  having,  in  conse- 
quence, a  firm  consistency  and  appearing  as  light  yellow  nodular 
deposits  ranging  in  size  from  that  of  a  potato  to  that  of  a  human 
head.  The  mammary  gland  in  dogs  is  another  frequent  site  for 
cystadenomata  and  combined  adenofibromata  or  for  transitional 
forms  becoming  cancerous.  In  the  lungs  adenomata  of  nodular 
form  may  originate  from  the  bronchial  mucous  glands,  obs-erved 
in  sheep  (A.  Eber)  and  horse. 

Although  in  man  mucous  membrane  polyps  occur  quite  fre- 
quently in  the  nose,  such  growths  are  more  uncommon  in  animals ; 
in  the  horse  they  are  met  hanging  into  the  naso-pharynx,  hyper- 
plasias perhaps  as  large  as  a  fist,  lobulated,  elongated,  slippery  and 
of  mucoid  consistence,  composed  of  soft  mucous  membrane  tissue. 
There  is  difficulty  in  trying  to  accurately  define  thyroid  adenomata. 
The  colloid  secreting  epithelium  of  this  organ  in  its  proliferation 
sometimes  gives  rise  to  a  general  enlargement  of  the  gland,  the  con- 


Adenoma.  393 

clition  known  as  goitre  (struma)  ;  and  sometimes  leads  to  nodular 
formations  which  originate  from  isolated  and  independently  growing 
cellular  foci  and  are  called  adenomata,  cystadenomata,  or  adenocar- 
cinomata,  but  which  are  usually  accompanied  by  diffuse  enlargement 
of  tlie  rest  of  the  parenchyma  of  the  organ.  In  the  same  way  pro- 
liferation of  the  glandular  tissue  of  the  ovary  and  testicle  is  usually 
diff\ise,  and  the  distinction  detween  hypertrophy  and  true  tumor 
formation  is  difficult  here  as  well  as  in  the  previous  example.  The 
cells  are  usually  of  an  indifferent  type  and  can  scarcely  be  distin- 
guished from  sarcoma  cells.  In  these  cases  the  terms  ovarioblastoma 
or  orchidoblastoma  are  convenient  names,  according  to  the  organ 
involved.  They  may  be  seen  as  solid  growths  or  with  cyst  forma- 
tion associated,  the  whole  organ  involved,  the  tumors  reaching  enor- 
mous size,  weighing  perhaps  ten  or  fifteen  kilograms  and  often  at- 
taining the  dimensions  of  a  human  head  or  even  twice  that  of  the 
full  stomach  of  a  horse  (in  horses,  cattle,  sheep). 

In  the  kidneys  true  adenomata  of  the  uriniferous  tubules  have 
never  been  observed.     The  tissue  proliferations  which  develop  here 
in  the  form  of  tumors,  as  a  rule  are  of  the  destructive  adenocarcino- 
matous  type  and  convert  the  organ  into  a  shapeless,  soft  material 
which  may  break  through  the  capsule.    This  substance  is  sometimes 
as  soft  as  marrow,  gray  to  brownish-red  in  color,  and  is  made  up  of 
large   canals   lined   by   cylindrical   epithelium.      In  other  cases   the 
growth   is  combined   with   sarcoma  and^  possibly  also  with  muscle 
fibres  and  constitutes  an  adeno-rhabdomyomatous  sarcoma  (Johne). 
[Some  of  the  tumors   described  as   renal   adenomata  are  in   real- 
ity hypcnicphroinata  (v.  p.  397)  ;  although  the  latter  growths,  which 
occur  in  the  kidney  as  their  most  frequent  seat,  are  ordinarily  easily 
distinguishable.     In  man  there  occasionally  are  seen  in  sections  of 
kidneys   small  isolated   foci  of  tubular  structure,  with  the  tubules 
either  small  and  compressed  or  at  places  distended  into  cystic  spaces. 
In  the  latter  papillary  proliferations  may  be  found  projecting;  the 
w'hole   appearance   corresponding   with   the   adenoma   papilliferum 
above  described.    In  these  cases  as  a  rule  the  foci  are  small,  perhaps 
microscopic,  and  the  general  picture  of  the  structures  suggests  their 
isolation   from  the  rest  of  the  tissue  by  an   inflammatory  change. 
Rarely  larger  nodules  of  this  character  are  met,  to  which  we  cannot 
refrain  from  applying  the  term  adenoma. 

The  prognosis  of  the  tumors  of  the  adenomatous  group  is  funda- 
mentally favorable ;  the  true  adenomata'  being  entirely  free  from  any 
tendency  to  infiltrate  or  to  give  rise  to  metastasis.  Such  growths 
are  harmful  merely  from  their  local  influences.     The  variety  above 


394  Tumors. 

mentioned  as  destructive  or  malignant  adenoma  or  adenocarcinoma 
is  essentially  cancerous  in  its  nature  and  is  malignant  both  bv  local 
extension  and  by  metastasis.  Any  adenoma  may  be  regarded  with 
suspicion  and  dealt  with  accordingly,  when  it  is  recalled  that  it  is  not 
very  uncommon  for  these  growths  to  lose  their  purely  adenomatous 
character  and  become  changed  into  adenocarcinomata.] 

Carcinomata. 

A  carcinoma  or  cancer  is  a  malignant  new  growth  composed  of 
epithelium  and  connective  tissue,  characterized  by  a  persistent  and 
progressive  penetration  of  its  epithelial  elements  into  the  underl>  ing 
tissues.  The  cancers  always  originate  from  epithelium,  either  surface 
epithelium  or  the  glandular  epithelial  cells  of  functionating  organs, 
or  from  islets  of  epithelial  cells  formed  in  foetal  life  and  occurring 
in  unusual  situations.  They  may  also  take  tlieir  origin  from  pre- 
viously existing  papillomata,  adenomata  and  cystomata,  these  having 
from  unknown  cause  assumed  a  proliferation  of  their  epithelial  cells 
with  departure  from  their  ordinary  forms  and  boundaries. 

The  proliferating  epithelium  forming  the  cancerous  parenchvma 
or  body  of  the  cancer  behaves  as  a  foreign  intruder ;  It  assumes 
an  independent  status  by  no  longer  remaining  confined  to  the  surface 
which  it  previously  covered,  breaking  through  its  normal  limiting 
structures  and  playing  the  part  of  epithelial  cells  which  have  be- 
come practically  parasitic.  These  cells,  derivatives  of  previously 
existing  epithelium,  by  their  penetrative  growth  and  active  multi- 
plication usually  form  in  the  deeper  structures  solid  cords  or  duct- 
like processes  which  branch  like  the  roots  of  a  tree  and  are  contin- 
ually sending  out  new  projections  into  the  tissue.  These  retain- 
ing their  continuity  with  each  other  result  in  forming  a  network 
or  meshwork  [of  epithelial  character  throughout  the  invaded 
tissue]  varying  in  its  density  and  with  irregular  nodal  point? 
(Ribbert).  This  net-like  and  corded  arrangement  of  the  epithelial 
roots  is  due  to  the  fact  that  the  cells  in  their  penetration  follow  the 
lines  of  least  resistance  and  therefore  penetrate  the  lumen  of  the 
lymph  passages,  come  to  completely  fill  them  with  their  growth  and 
therefore  to  assume  their  shape.  After  occupying  all  the  lymph 
spaces  of  the  connective  tissue  the  epithelial  roots  may  penetrate 
into  the  tissue  itself  in  such  numbers  as  to  practically  constitute  a 
difl-'use  infiltration   (Ribbert). 

In  microscopic  sections  the  continuity  of  the  cords  is  not  entirely  appre- 
ciated, as   each   sectional   layer,  of   course,   contains   only   segments   of   them. 


Cancer.  395 

In  serial  sections  or  in  plastic  reconstruction  of  tlie  general  tumor-picture 
by  means  of  the  methods  of  planar  modeling,  one  may  always  convince 
himself  of  the  interconnection  of  all  the  epithelial  cords   (Diirk). 

The  connective  tissue  of  the  organ  in  which  the  epithelial  cells 
are  in  active  cancerous  proliferation,  does  not,  however,  act  in  a 
purely  passive  manner,  as  a  tissue  shoved  aside  and  compressed  by 
the  epithelial  growth ;  but  reacts  by  an  inflammatory  change  which 
in  its  chronic  course  leads  to  tlie  production  of  a  connective  tissue 
hyperplasia.  The  epithelial  masses  act  precisely  like  foreign  bodies, 
attract  leucocytes  to  them  1)y  chemotaxis,  the  latter  cells  collecting 
about  the  margins  of  the  epithelium  just  as  in  a  demarcating  inflam- 
mation and  sometimes  producing  a  marked  cellular  infiltration  of  the 
connective  tissue.  At  the  same  time  the  fixed  connective  tissue  cells 
proliferate  and  form  a  fibrous  stroma  (framework  of  the  cancer) 
of  varying  texture,  containing  young  bloodvessels  and  enclosing  epi- 
thelial nests. 

The  distinction  from  the  typical  fibroepithelial  tumors  [adenoma, 
papilloma]  lies  in  the  fact  that  in  the  latter  the  epithelium  and 
connective  tissue  are  united  in  common  growth  to  form  a  tissue  com- 
plex, a  compound  tumor  basis  ;  while  in  cancer  in  reality  only  the 
epithelium  is  the  basic  tumor  element,  and  the  connective  tissue 
growing  along  with  it  is  the  result  of  a  productive  inflammation  and 
belongs  properly  to  the  organ  in  which  the  cancer  is  located.  The 
cancer  stroma  therefore  is  but  the  interstitial  tissue  of  the  affected 
organ,  involved  bv  inflammation.  The  epithelial  elements  of  the 
cancer  develop  in  the  organ  in  which  the  tumor  originally  (prim- 
arily) gre\v,  from  cells,  it  is  true,  already  present  therein  ;  but  the 
epithelial  cells  of  the  organ  are  not  uniformly  changed  into  cancer 
cells,  do  not  all  take  part  in  the  tumor  construction.  The  growth 
and  extension  of  the  latter  involves  invariably  a  fixed  group  of  cells 
acting  as  the  germinal  elements  of  the  tumor,  toward  the  multipli- 
cation of  which  the  other  epithelial  cells  remain  passive. 

The  microscopic  studies  of  Ribbert  have  furnished  a  number  of 
considerations  which  concern  the  histological  production  of  the  pri- 
mary stage  of  this  type  of  tumor,  the  start  of  the  cancer  formation. 
Ribbert  refers  the  origin  of  the  growth  to  an  isolation  from  the  cel- 
lular union  in  an  organ  of  individual  epithelial  cells  or  a  group  of 
cells,  as  an  epithelial  ingrowth,  a  separated  bit  of  epiderm,  or  a 
lobule  of  a  gland :  this  subsequently  assuming  independent  prolifer- 
ation. This  isolation  from  physiological  connection  is  usually 
brought  about,  as  Ribbert  recognized  in  microscopic  sections  in  the 


396  Tumors. 

initial  stages  of  skin  cancers,  by  the  intrusion  of  connective  tissue, 
stimulated  to  proliferation  by  inflammation,  between  the  epithelial 
cells.  In  other  words,  according  to  Ribbert  cancers  always  start  on 
a  base  of  chronically  inflamed  tissue.  The  epithelial  cells  do  not 
make  the  initial  penetration  into  unaltered  connective  tissue ;  the 
primary  change  being  the  inception  of  the  inflammatory  prolifera- 
tion of  the  subepithelial  connective  tissue,  which  raises  the  epithe- 
lium and,  as  the  proliferating  connective  tissue  elements  invade  the 
deeper  epithelial  layers  and  destroy  the  intercellular  cement, 
separates  isolated  cells  from  their  proper  relations  and  thus  mis- 
places them.  The  isolated  epithelium,  now  situated  in  the  midst 
of  the  connective  tissue  and  sufficiently  nourished  by  it,  begins 
to  nuiltiply ;  and,  being  prevented  from  growing  upward  toward 
the  surface  of  the  skin  or  mucous  membrane,  and  its  relations  with 
the  general  epithelial  tissue,  its  nerves  and  normal  substratum 
(papillary  layer)  being  destroyed,  it  must  necessarily  penetrate 
irregularly  into  the  tissues  along  the  course  of  the  lymph  spaces. 
Thus  it  comes  to  force  its  radicles  and  cords  in  every  direction 
and  to  form  the  beginning  of  the  cancer. 

As  a  matter  of  fact  cancers  do  occur  with  frequence  in  places 
where  for  some  time  previously  inflammatory  irritation  has  existed. 
In  man,  for  example,  cancer  of  the  lip  is  especially  likely  to  be  met 
in  persons  who  smoke  pipes  habitually,  and,  too,  just  in  the  corner 
of  the  mouth  which  is  always  exposed  to  irritation  from  the  juices 
from  the  pipe.  The  influence  of  soot  as  an  irritant  capable  of  in- 
ducing cancer  is  well  seen  in  chimneysweeps  (chimney  sweep's  can- 
cer) ;  and  that  of  paraffine  has  become  well  known  among  the  em- 
ployees of  parafline  factories  as  causing  epidermoidal  proliferations 
(paraffine  cancer  of  tlie  hands).  A.  Sticker  has  called  attention  to 
several  examples  which  indicate  a  causative  relation  of  external 
influences  upon  the  establishment  of  cancer,  as  the  occurrence  of 
skin  cancer  in  cattle  after  branding  (Mac  Fadyan),  and  beneath  the 
chin  in  swine  from  chaffing  (Eggeling).  Possibly  the  frequence  of 
cancer  of  the  anus  of  dogs  has  some  connection  with  external  inju- 
ries (from  the  animal  scraping  the  anal  region  along  the  ground,  so- 
called  "sleigh-driving"). 

The  origin  of  cancer  should  not,  therefore,  be  attributed  to  any 
one  cause,  as  a  definite  cancer  parasite  or  an  infectious  agent,  but 
may  be  determined  from  any  influence  (traumatic,  chemical,  infec- 
tious) which  occasions  chronic  inflammation  and  because  of  which, 
as  a  result  of  the  inflammatory  process,  an  isolation  of  the  living 


Cancer.  397 

epithelial  cells,  retaining  their  power  of  proliferation,  occurs.    It  is 
of  course  true  that  inflammations  of  surfaces  covered  by  epithelium 
and  epithelial  organs  are  frequently  seen  without  resultant  cancer 
production,    even   though   it   may   be   presumed   that    isolations   of 
epithelial  cells  may  often  obtain  in  connection  with  these  processes. 
But,  as  Ribbert  insists  in  case  of  such  exceptions,  much  depends 
upon  the  length  of  time  over  which  the  inflammation  extends.     In 
acute  inflammations  the  epithelium  is  apt  to  be  injured,  and  even  if 
isolated  cells  be  misplaced  in  the  subjacent  tissues  the  process  is  of 
too  short  duration  to  allow  the  cells  to  accommodate  themselves  to 
their  new  surroundings;  they  therefore  perish   (Ribbert).     In  the 
same  way  as  an  inflammatory  connective  tissue  production,  epithe- 
lial cells  may  in  papillary  and  polypous  new*  growths  be  cut  off  and 
isolated   by   the    proliferation    of   the    stroma,    or    whole    cores    or 
bunches  of  them :  and  thus  a  primarily  benign  tumor  may  be  con- 
verted into  a  malignant   one  by  the   progressive   growth   of   such 
cells   into   the   underlying   tissues.      The   change   of    fibroepithelial 
growths  which  for  years  have  been  of  simple  type  into  destructive 
cancers    is   a   well   authenticated    observation    in   human   medicine. 
Finally,  epithelial  misplacements,  which  may  accidentally  be  caused 
in  foetal  life  in  the  processes  of  arrangement  of  the  various  tissues, 
in    the    formation    of    folds    and    cavities    which   are    taking   place 
among  the  tissues  in  the  construction  of  the  various  organs,  may 
furnish  the  original  substance  for  a  subsequent  cancer. 

A  good  example  of  this  is  afforded  by  the  nodular  growths  met  in  the 
human  kidney  cortex,  originating  from  misplaced  adrenal  tissue.  They  are 
met  as  single  or  multiple  growths,  well  defined;  and  sometimes  destroy  the 
kidney,  penetrate  into  the  blood  vessels,  and  give  rise  to  fatal  metastasis. 
These  nodes  are  of  a  yellowish  color  from  the  fat  which  they  contain,  and 
under  the  microscope  are  seen  to  be  made  up  of  cords  of  cells  arranged 
in  parallel  lines  along  the  blood  vessels,  and  resembling  in  their  appearance 
the  epithelium  of  the  suprarenal  bodies  (hypernephroma,  adrenal  cancer). 
LThese  growths  are  also  met  with  not  very  infrequently  in  the  kidneys  of 
cattle  and  occasionally  in  hogs;  they  are  not  confined  to  the  kidney,  but 
may  be  found  in  any  of  the  structures  near  the  adrenals  or  in  the  adrenals 
themselves,  where  they  may  either  represent  foetal  rests,  or  may  have  started 
from  isolated  parts  or  inclusions  of  the  tissue  of  the  organ  caused  by  inflam- 
matory sejparations.] 

Ribbert's  attempted  explanation  of  the  genesis  of  cancer  is  not 
as  vet  accepted  by  many  pathologists.  Inflammatory  changes  are 
often  not  demonstrable  at  the  places  of  origin  of  cancers ;  and  some 
authors  do  not  believe  that  the  atypical  proliferation  of  the  epithe- 
lium is  a  result  of  the  invasive  growth  of  the  comiective  tissue  but 


39^  Tumors. 

that  some  otlier  as  yet  unknown  causes  underlie  the  irregular  pro- 
gressive proliferation  which  these  cells  manifest  (in  other  words, 
that  the  epithelial  multiplication  is  the  primary  process)  ;  and  search 
lor  some  kind  of  infectious  agent  is  not  as  yet  abandoned.  The 
occasional  endemic  occurrence  of  cancer  (also  observed  bv  Eggel- 
ing  in  hogs  in  a  certain  locality)  and  isolated  cases  which  suggest 
the  transmissibility  of  certain  forms  of  cancer  continue  to  keep  the 
question  of  the  infectiousness  of  cancer  in  discussion.  A.  Sticker, 
for  example,  has  called  attention  to  a  dog  which  for  a  long  time 
liad  been  in  the  habit  of  lying  by  the  bed  of  a  man  suffering  from 
cancer  of  the  stomach  and  ate  all  sorts  of  material  which  the  man 
had  vomited,  and  which  became  affected  by  a  general  carcinomato- 
sis (lungs,  liver,  omental  sac.  but  not  the  alimentary  canal).  This 
may  have  been  a  mere  coincidence,  but  the  possibility  of  an  etio- 
logical relationship  between  the  two  cases  cannot  be  entirelv  ig- 
nored. ( Cf.  p.  334. )  Experimental  attempts  to  prove  an  infectious 
nature  as  existing  in  these  growths  (inoculation  and  feeding  ex- 
periments) have  hitherto  always  failed.  Trasbot  obtained  no  posi- 
tive result  from  hundreds  of  such  attempts :  Duplay  and  Cazin 
failed  in  over  one  hundred  and  twenty  experiments  in  dogs  and  rats ; 
Gratia  and  Lienaux,  Cadiot  and  Gilbert  had  no  more  success  in 
numerous  attempts  to  transmit  tliese  tumors,  employing  all  sorts 
of  methods  of  inoculation  (from  dog  to  dog,  from  man  to  dog). 
The  transplantation  of  certain  forms  of  cancer  in  rats  and  mice  has 
alone  succeeded  (Hanau.  ]\Ioraus.  C.  O.  Jensen)  :  but  the  methods 
employed  do  not  indicate  that  an  infectious  agent  was  operative^ 
but  rather  that  the  cells  of  the  cancer  used  in  the  experiment  were 
capable  of  multiplying  if  placed  in  uninjured  condition  in  a  new 
specifically  similar  soil  (i.  e.,  transplanted  to  the  same  species  of 
animal  as  that  from  which  derived),  and  of  continuous  develop- 
ment into  an  independently  growing  tumor  tissue  in  their  practically 
parasitic  colonization  and  multiplication,  (cf.  Definition  of  tumors 
P-  325-)  [Transplantation  of  cancers  in  animals  has  invariably 
shown  that  success  is  to  be  expected  only  when  the  animal  to  which 
the  tumor  is  transplanted  is  of  the  same  species  as  that  from  which 
it  was  derived,  even  varieties  of  the  same  species  making  the  result 
doubtful.  In  this  country  Leo  Loeb,  Gaylord,  Herzog  and  others 
have  carried  various  cancerous  growths  or  mixed  cancers  through  a 
number  of  generations  in  rats  and  mice.  In  these  experiments  actual 
portions  of  the  living  growth  (bits  may  retain  life  for  some  hours 
-when  kept  in  moderate  refrigeration  after  removal  from  the  origi- 
nal animal)   must  be  introduced   into  the  experiment  animals  and 


Cancer.  399 

filtered  extracts    arc    not    followed    by    success.     Ehrlich    {Berlin. 
Klin.   Woehenschr.,  No.  28,   1905;  Xo.  2,   1906)   and  Loeb   {Univ. 
of  Penna.  Med.  Bull.,  July,  1905)  have  both  recorded  the  occurrence 
of    sarcoma    succeeding    the    original    carcinomatous    tumors    after 
some   generations   of   transmissions.      This    would    not    necessarily 
suggest  the   direct  transformation  of   the  cancer  into  sarcoma,  as 
much  as  that  in  the  course  of  growth  the  proliferating  epithelium 
had    induced    such    changes    in    the    connective   tissue    portions    of 
the   lumr)r   as  to   cause   them   to  acquire  an   analogous  energy   of 
atypical   proliferation,  and  that  perhaps  this  latter  tissue  or,  what 
perhaps     is     more     ])robable,     immune     bodies,     reactively     de- 
veloping to  the  cancer,  have  caused  the  disappearance  of  the  epi- 
thelium  itself.     The  known   spontaneous  disappearance  of   cancers 
(cf.    Gaylord    and    Clowes :    Sitrgcry,    Gynecology   and    Obstetrics, 
June,  1906)  speaks  in  favor  of  the  existence  of  such  cytolytic  factors. 
Gaylord's  success  in  obtaining  a  serum  from  mice    spontaneously 
recovering  from  cancers,   which  on  injection   into  mice  having  in 
their   bodies    actively   growing   tumors   of    the   same   strain   cawses 
them  to  recover,  speaks  in  the  same  line ;  and  the  fact  that  an  ex- 
tract of  a  tumor  (v.  p.  339)  injected  into  the  body  of  the  original 
animal  having  other  nodes  of  the  same  growth  in  its  body,  strongly 
supports  the  same  idea.     Tentatively  then  it  may  be  held  that  in  case 
of  cancers  at  least  the  present  tendency  is  not  so  much  to  accept  the 
existence  of  a  specific  parasitic  cause  for  the  growth  as  to  believe 
that  once  established  as  an  independent  focus  of  growth  by  some 
such  method  as  is  suggested  in  Ribbert's  isolation  theory,  the  epi- 
thelial cells  become  themselves,  as  it  were,  practically  parasitic  in 
the  organism  of  which  they  were  once  an  integral  part :  that  they 
grow  as  parasites  and  act  as  parasites  :  and  that  the  body  reacts  to 
their  presence  as  it  does  to  other  parasitic  organisms,  and  endeav- 
ors  (sometimes  successfully)   to  produce  cytolytic  or  other  protec- 
tive  reactions  which   will  tend  to  destroy  the   cancer   cells.     This 
view  opens  an  attractive  and  wide  field  for  application  in  many  lines, 
not  merely   therapeutic,   and   suggests   reasons   which  may   explain 
the  special  prevalence  or  special   failure  of  secondary  growths   in 
different  systems  and  organs  of  the  body,  as  it  may  be  supposed 
that  all  parts  are  more  or  less  open  by  the  lymph  or  blood  streams 
to  the  reception  of  secondary  tumor  emboli.] 

All  other  contributions  dealing  with  cancer  parasites  (cancer 
bacilli,  blastomycetes,  etc.)  recognized  by  microscopic  methods  have 
originated  from  mistaken  interpretations  of  the  microscopic  pic- 
tures presented  in  various  examples. 


400 


Tumors. 


The  dissemination  of  the  cancer  into  the  tissues,  as  above  indi- 
cated, occurs  primarily  from  the  penetration  of  the  multiplying  epi- 
thelium into  the  lymph  spaces.  They  here  form  tubular  or  solid 
laminated  cords,  push  aside  the  endothelium  and  other  connective 
tissue  elements,  and  by  continuous  progression  of  growth  force  their 
way  deeper  into  the  tissues,  between  the  muscle  fibres  and  beyond. 
In  this  way,  for  example,  a  growth  on  the  surface  of  a  mucous 


Fig.  118. 
Lung  of  dog  with   metastatic  cancer  nodes    (tliyroid   cancer). 

membrane  forces  its  way  through  the  muscularis  mucosa  and  onward 
into  the  muscular  tunics  and  serous  coat  of  the  tube.  In  the  lymph 
passages,  by  continuity  of  growth  the  cords  of  cancer  cells  may 
extend  as  far  as  the  nearest  lymph  glands ;  or  individual  cells  loos- 
ened in  some  way  may  be  carried  by  the  lymph  current  to  the  latter 
and  to  more  distant  portions  of  the  lymphatic  system.  Multiplica- 
tion of  the  tumor  cells  in  the  tissue  of  the  lymph  nodes,  and  the  re- 
active inflammatory  proliferation  of  the  connective  tissue  of  these 


Cancer.  401 

structures,  lead  to  marked  chronic  enlargement  of  the  glands 
(lympJwgciioiis  cancer  metastases),  one  of  the  clinical  character- 
istics of  the  cancerous  affection.  Passing  from  the  lymph  glands 
the  cells  of  the  growth  may  hy  following  the  course  of  the  efferent 
lymph  vessels,  pass  into  the  blood  (anterior  vena  cava)  ;  or  they 
may  gain  entrance  to  the  blood  by  direct  penetration  of  the  blood 
vessel  wall  in  their  growth.  In  either  event  the  cells  are  carried 
onward  with  the  blood  stream  and  form  new  foci  wherever  they 
may  lodge  in  the  capillaries  and  give  rise  to  the  formation  of  nodes 
(hcrmatogeiious,  eiiibolic  cancer  metastases). 

]\Ietastatic  nodes  are  as  a  rule  round,  and  multiple  or  dissemi- 
nated because  the  cells  have  been  widely  scattered  through  an  ex- 
tensive area  of  vascular  distribution.  As  a  rule  they  are  first  sit- 
uated in  the  lungs,  because  the  cells  are  very  likely  to  penetrate 
into  a  vein  and  be  carried  throiigh  the  right  heart  and  into  the 
lungs ;  in  case  of  primary  cancer  of  the  stomach,  intestine  or  pan- 
creas the  liver  is  apt  to  be  involved,  by  convection  through  the  por- 
tal vein.  Should  isolated  cells  pass  through  the  pulmonary  capil- 
laries and  get  into  the  general  circulation  b}-  way  of  the  leff  heart, 
other  portions  of  the  body,  as  the  spleen,  kidneys  or  bones,  may  be 
involved  by  dissemination  of  the  metastatic  cells.  Sometimes,  too. 
when  these  cells  .penetrate  into  bloodvessels  they  grow  into  cord- 
like processes  along  the  vascular  lumen ;  solid  plugs  of  cancer  cells 
as  thick  as  lead  pencils  may  occasionally  be  found  extending  in 
the  thyroid  veins  from  a  cancer  of  the  thyroid  gland,  even  down 
into  the  thoracic  cavity.  The  vascular  lumen  becomes  more  or  less 
obstructed  and  the  secondary  thrombi  formed  are  verv  likclv  to  be 
invaded  by  the  cancer  cells. 

As  the  tumor  enlarges  it  compresses  and  pushes  aside  all  the 
elements  of  the  organ  with  which  it  comes  in  contact ;  in  their  pene- 
tration into  the  deeper  tissues  and  by  their  lateral  extensions  the 
cellular  roots  of  the  cancer  distend  and  occupy  the  lymph  spaces, 
pushing  aside  whatever  gland-tissue,  muscle  or  nerve  may  be 
present,  spreading  out  beneath  the  epithelial  covering  of  mucous 
membranes  or  integument  and  perforating  layers  of  epithelium  which 
they  may  encounter.  Pressure  atrophy  and  necrosis  of  the  surround- 
ing tissue  and  tissue-destruction  from  the  accompanying  inflamma- 
tion result  from  the  cancerous  infiltration,  even  hard  bone  and 
cartilage,  perhaps,  being  broken  down  by  these  changes.  As  the  tu- 
mor tissue  nniltiplies  beneath  the  epithelial  la\  er  of  a  surface  it  raises 
it  up,  spreads  out  in  larger  and  larger  area   close  to  the  surface 


402 


Tumors. 


and  develops  in  nodular  prominences.  By  cropping  out  on  the 
surface,  by  perforation  at  one  or  more  places  of  such  a  protuber- 
ance, it  ma}'  become  a  direct  surface  growth  with  nodulated,  uneven, 
undulating  elevations  and  more  or  less  fissured  surface.  The  in- 
flammatory infiltration  of  the  stroma,  exaggerated  by  the  entrance 
of  extraneous  irritants  into  the  exposed  growth  (contact  with  air, 
intestinal  contents,  dirt  or  bacteria),  is  likely  in  such  event  to  bring 
about  an  ulcerative,  foully  suppurating  destruction  of  the  surface 
of  the  cancer  (cancerous  ulcer).  In  case  of  penetration  into  asep- 
tic cavities,  especially  the  peritoneal   (gastric  cancer,  cancer  of  the 


Fig.   110. 
Cancer  of  tail  of   cow. 

intestine,  cancer  of  kidney),  transplantation  of  epithelial  cells  loos- 
ened from  the  growth  may  be  brought  about  by  the  intestinal  peris- 
talsis (by  movements  of  the  lungs,  diaphragm  and  heart  in  the 
chest)  and  give  rise  to  extensive  secondary  carcinomatosis  in  the 
serous  membranes  by  their  growth.  The  secondary  formations  are 
at  first  small  grayish-white  nodules  (iiiiliary  carcinomatosis),  but 
later,  by  confluence  of  the  enlarging  cancerous  foci  and  the  accom- 
panying inflammatory  changes,  a  diffuse  cancerous  peritonitis  or 
pleuritis  may  be  established. 

The  morphology  of  the  epithelial  cells  of  which  a  cancer  is  com- 
posed  corresponds   in   a  general   way   wifli    that   of   the  epithelium 


Cancer. 


403 


from  which  the  tumor  took  its  orig-in ;  in  a  greater  or  less  measure 
the  cancer  cells  preserve  the  peculiarities  of  the  epithelium  of  the 
place  of  inception,  -as  a  tendency  to  kcratinization,  to  formation  of 
mucin  and  other  secretory  substances.  This  retention  of  original 
characteristics,  which  is  well  seen  in  the  metastatic  nodes,  often 
makes  it  possible  to  determine  from  microscopic  examination  the 
primary  source  or  origin  of  a  cancer.  This  is,  however,  often  sub- 
ject to  modification.  The  growth  of  epithelial  cells  in  unfamiliar 
positions,  their  separation  from  their  normal  substructures,  must 
directly,  because  of  the  altered  nutritional  conditions  and  the  vari- 
ous factors  of  tissue  resistance,  occasion  variation  in  their 
shape  and  size.  In  consequence  we  often  ^neet  with  morphological 
variations  and  anomalies  which  differ  so  widely  from  the  original 


Fig.  120. 

Cancer   of   glans   penis   of   horse. 


characteristics  of  the  mother  cells,  that  it  may  be  quite  impossible 
to  come  to  any  conclusion  as  to  the  source  and  type  of  the  tumor 
from  the  morphology  of  its  individual  cells.  In  addition  to  this 
polymorphism  of  the  cancer  cells  there  may  also  occur  one  or  other 
of  a  variety  of  retrograde  metamorphoses  in  the  luxuriantly  growl- 
ing and  irregularly  nourished  cells,  rendering  them  completely  un- 
recognizable ;  so  that  at  times  the  real  character  of  the  cellular  ele- 
ments can  be  made  out  only  in  the  more  recent  parts  of  the  tumor. 

Corresponding  to  the  major  types  of  cutaneous,  mucous  mem- 
brane and  glandular  epithelium,  three  classes  of  cancers  may  with 
Diirk  be  recognized : 

I — Surface  cell  cancers  of  the  skin  and  mucous  nuvnhranes  cov- 
ered -with  flat  epithelium  (called  brietly  by  most  authors  squamous 
epitheliomafa.) 


404 


Tumors. 


2 — Surface  cell  cancers  of  nnicoiis  meuihranes  covered  with  cyl- 
indrical epithelium  (cylindrical  cell  cancers). 

3 — Glandular  cell  cancers  [carcinomata]. 

Squamous  epitheliomata,  originating  from  the  skin  and  mucous 
membranes  covered  with  squamous  epitheUum,  manifest  their  epi- 
theUal  proHferation  by  forming  soHd  cords  of  cells  penetrating  the 
deeper  tissues,  these  cords  for  the  most  part  made  up  of  cells  of  the 
type  found  in  the  stratum  ^Nlalpighii.  The  prickle  and  ridged  borders 
of  the  cells,  the  protoplasmic  processes  extending  through  the  in- 


Fig.   121. 

Secondary    carcinomatosis    of    serous    surface    of    liver    and    omentum    of    horse ; 
primary  growth  of  cancer  in  the  ovary. 

tercellular  cement  (so-called  intercellular  bridges)  are  usually  well 
marked,  and  the  cells  are  arranged  in  layers  as  over  the  papillary 
layer  of  the  cutis  ;  and  in  consequence  we  usually  find'  the  cells  next 
to  the  stroma  of  the  tumor  of  a  cylindrical  form,  the  next  layers 
cubical,  and  the  inner  parts  of  the  cord  occupied  by  squamous  cells. 
The  epithelium  in  its  growth  has  no  opportunity  for  desquamation 
in  these  connective  tissue  spaces,  and  the  old  and  first  formed  layers 
must  necessarily  be  found  in  the  central  part  of  the  plug-like  cord ; 
being  derivatives  of  epithelium  subject  normally  to  keratous 
change,  the  cells  of  a  squamous  epithelioma  usually  also  undergo 


Cancer. 


405 


keratinization,  and  here,  to(\  the  change  affects  the  older  cellular 
elements.  The  interior  of  the  cancer  roots  show  these  fiat  cells, 
homogeneous  and  staining  diffusely  with  eosin  or  fuchsine,  with 
their  nuclei  poorly  shown  or  entirely  lost,  precisely  as  those  of  the 
surface  of  the  epiderm.  In  consequence  on  cross  section  an  onion- 
like concentric  lamination  of  the  cells  is  apparent,  with  the  cells 
bent   in   crescentic  manner  and   applied  upon  each  other  like  flat 


Fig.  122. 

Microscopic    section    of    a    sqiiainons    epithelioma    of   urinary    lilaclder    of    cow    (low 
power).     Epithelial  cords  have  grown  in  between  the  saiootli  muscle  fibres. 


scales.  These  horny  plugs  can  sometimes  be  picked  out  entire  with 
the  knife  and  are  called  cancer  pearls  ["pearly  bodies,"  "squamous 
cell  or  concentric  nests"].  The  arrangement  of  layers  otherwise 
is  apt  to  be  quite  irregular,  the  composite  network  of  epithelial 
roots  forming  at  places  broad,  thick  masses  with  wavy  outline,  at 
others  delicate,  line-like  threads. 

The  stroma  of  the  squamous  cell  cancer,  present  in  varying  pro- 
portions in  dift"erent  cases,  is  usual!}-  the  seat  of  a  marked  round 


4o6 


Tumors. 


cell  infiltration,  a  true  inflammatory  infiltration;  and  the  wandering 
cells  may  be  found  penetrating  even  into  the  epithelial  plugs. 

In  cylindrical  cell  cancers  the  cylindrical  epithelium,  extending 
in  its  proliferation  into  the  deeper  tissues,  laterally  and,  together 
with  its  connective  tissue,  also  superficially,  usually  forms  gland- 
like tubes  which  branch  out  in  different  directions  as  narrow  or 
wide  hollow  oft'shoots.     The  proliferating  columnar  cells  may  re- 


Fig.  123. 
Microscopic    section    of   a    siiiiamous    epithelioma    of   glans    penis   of   liorse. 

main  in  a  single  layer  or  become  stratified,  in  the  latter  case  under- 
going various  changes  in  shape  corresponding  with  the  prevailing 
pressure  conditions,  goblet  cells  peculiar  to  the  mucous  membrane 
often  being  met  in  great  numbers. 

Glandular  cell  cancers,  as  far  as  the  morphology  of  their  cells 
is  concerned,  are  as  varied  as  the  types  of  cells  in  the  different 
glands  of  the  body.  As  in  adenomata,  in  these  growths  the  specific 
gland  tissue   repeats   itself  in   tumor  form.     The   retention  of   the 


Cancer. 


407 


tubular  arraugement  of  the  cells,  and  the  simple  (one  layer)  lining 
of  these  tubes  may  so  well  preserve  the  gland  pattern  that  the  name 
adcno-carciiioiiia  has  been  applied  to  these  and  to  the  tubule-forming 
cylindrical  cell  cancers.  The  resemblance  to  the  original  gland  may 
be  so  great  that  not  merely  the  morphology  of  the  most  of  the  tumor 
cells  remains  unchanged,  hut  even  the  production  of  secretory  sub- 
stances in  the  tumor  tissue  is  distinctly  analogous.  Thus  hepatic 
cancers  have  epithelial  cells  of  precisely  the  same  type  as  the  polygo- 


PI 


S~4^^ 


^^^^'         v^^-^^ 


Fig.   124. 

Microscopic    section    (if    adenocarcincma    of    icidney    of    horse. 


nal  hepatic  cells,  arranged  in  anastomosing  trabecular  columns,  with 
capillaries  and  scanty  connective  tissue  extending  between  them ; 
and  these  epithelial  cells  secrete  bile,  the  tumor  sometimes  being 
stained  an  intense  yellow  or  green  color  from  the  latter.  Thyroid 
cancers,  made  up  of  low.  cubical,  thyroid  epithelial  cells  and  a  vas- 
cular stroma,  show  as  a  rule  a  practical  duplication  of  the  structure 
of  the  thyroid  gland  in  the  production  of  colloid  material  and  in 
the  alveolar  distension  of  their  epithelial  ofifshoots.  Cancers  of  the 
intestinal   glands   repeat   the   tubular   invaginations   of   the    Lieber- 


4o8 


Tumors. 


kiihn's  crypts  with  of  course  considerable  enlargement  of  the  lumina, 
and  are  characterized  l)y  marked  production  of  mucin  and  by  the 
presence  of  numerous  goblet  cells  among  the  lining  epithelium. 
Mammary  cancers  have  so  marked  a  tendency  to  *fat  formation  from 
their  cells  arranged  in  alveoli,  that  milk-like  fluid  is  usually  found 
filling  the  tubular  cancerous  spaces ;  and  ovarian  cancers  undergo 
the  formation  of  cysts  which  might  well  be  mistaken  for  the 
follicles. 


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Hard  adenocarfiuoma  of  mammary  gland  of  a  Ijitcli ;  shows  the  predominance  of 
the  connective  tissue  stroma,  the  preservation  of  duct  and  acinous  arrange- 
ment of  epithelium  (as  at  a),  but  also  the  irregular  and  excessive  epithelial 
formation  of  solid  cords  and  infiltration  of  tissues  by  their  penetrating 
anastomoses    (as  at  b). 


The  same  structure,  too,  is  repeated  in  the  metastatic  nodes  in 
the  lungs,  peritoneum  and  elsewhere,  proving  their  derivation  from 
the  primary  tumor  and  its  original  source. 

This  correspondence  in  cellular  character  between  the  carcinoma 
and  the  gland  from  which  it  originated  is,  however,  not  always  ap- 
parent, the  atypical  nature  of  the  growth  manifesting  itself  in  the 
extension   of   the   cells   beyond    their   normal    limiting  membranes, 


Cancer.  409 

their  dissemination  in  the  surrounding  tissue  and  their  metastasis, 
and  in  the  fact  that  the  epithelial  outgrowths  do  not  form  com- 
pletely hollow  passages,  but  are  seen  in  massive  proliferation  as 
solid  cellular  roots.  The  ducts  of  the  involved  structure  are  filled 
with  epithelium,  and  Uie  cells  show  a  great  variety  of  altered  shapes 
depending  upon  the  pressure  conditions  prevailing,  fusiform, 
rounded,  irree:ular.  etc.  The  connective  stroma  varies  much  in  its 
degree  of  development,  and  is  sometimes  found  in  villous  masses,  in 
folds  and  laminated  processes  just  as  in  adenomata,  especially  when 
there  are  spaces  and  large  cavities  in  the  tumor  {cyisto carcinoma 
papular  e). 

[The  essence  of  the  histological  fault  of  any  cancer  lies  in  the 
fact  that  in  its  proliferation  the  epithelium  of  the  tumor  does  not 
maintain  its  normal  topographical  relations,  but  grows  tlirough  its 
limiting  membrane  and  is  found  infiltrating  to  a  greater  or  less 
desfree  the  tissue  about  it,  either  as  isolated  cells  or  as  roots  or  cord- 
like  groups  of  cells.  In  most  cases,  too,  increase  in  the  amount  of 
epithelium  is  recognizable  not  only  by  this  infiltrative  or  metastatic 
excess  but  by  an  excessive  number  of  cells  upon  the  surface  in- 
volved, or  within  the  tubular  spacer  or  the  alveoli  of  the  afifected 
portion  of  the  gland ;  thus  instead  of  a  single  layer  of  cells  lining  the 
tubular  canals  of  a  cancerous  area  of  endometrium,  it  is  common 
to  find  a  number  of  layers  and  the  tubules  distended  and  branched 
as  the  author  above  indicates.  This  excess,  however,  is  by  no  means 
an  essential  feature,  many  scirrhous  carcinomata  showing  a  mani- 
fest reduction  in  the  epithelial  elements  below^  that  realized  as  nor- 
mal to  the  original  gland  and  to  the  ordinary  cancers  of  the 
same  organ ;  and  in  such  cases  one  finds  not  only  relatively  few 
epithelial  areas  but  also  no  excess  of  layers  in  the  tubular  lumina, 
the  cells  which  do  line  such  spaces  being  in  fact  themselves  small, 
atrophic  or  degenerative.  It  will  be  found,  however,  that  many  of 
the  cells  in  these  have  no  relations  to  tubes  or  alveoli  and' are  clearly 
free  in  the  lymph  spaces  of  the  connective  tissue  stroma;  and  care- 
ful examination  of  the  gland-like  spaces  or  tubes  will  somewhere 
show  the  direct  gro\vth  of  the  epithelium  into  the  surrounding 
tissue  beyond  the  proper  membrane.  The  existence  of  karyokinetic 
nuclear  figures  is  of  some  value  as  indicating  the  active  prolif- 
erating state  of  the  epithelium. 

.  The  editor  believes  that  for  practical  purposes  in  microscopic 
diagnosis  of  cancers  of  the  author's  two  varieties,  cylindrical  cell 
and  glandular  cell  cancer,  it  is  appropriate  to  recognize  two  types 
according  to  the  existence  or  non-existence  of  marked  resemblance 


^ 


410 


Tumors. 


to  glands.  Those  cancers  which  exhibit  a  distinct  tubular  or  acinous 
structure  (from  which,  however,  the  deviations  just  indicated  are 
evident)  are  adciiocarciiwinafa.  All  of  the  types  of  cancer  here 
under  discussion  may  be  said,  at  least  in  their  early  period,  to  be 
adenocarcinomata.  Those  in  which  the  proliferative  and  infiltra- 
tive processes  have  so  advanced  as  to  destroy  the  original  gland 
resemblance,  so  that  definite  tubes  or  acini  are  not  well  or  numer- 
ously recognizable,  may  well  be  called  carcinoiiia  simplex.  These 
merely  represent  more  advanced  stages  of  the  first,  and. are  more 
common  as  actively  growing  and  extending  cancers. 

The  stroma  of  true  cancer,  as  the  author  remarks,  is  exceedingly 
variable  and  is  often  the  basis  for  special  sub-divisions  of  the 
growths.  Thus  it  may  be  relatively  small  in  amount,  the  epithelial 
elements  predominating ;  this  condition  underlies  the  group  of  soft 
cancers  (medullary  cancers).  Or  it  may  be  greatly  in  excess, 
markedly  predominating  over  the  epithelium  of  the  growth,  dense 
and  fibrous ;  such  growths  are  the  well  known  hard  cancers  or 
scirrhous  cancers  (substantive  scirrhns).  The  connective  tissue 
stroma  may  exceptionally  be  found  largely  or  totally  of  a  gela- 
tinous type  {carcinoma  myxomatodes)  ;  or  highly  cellular  and  evi- 
dently of  a  sarcomatous  type  {carcinoma  sarcomatodes).  Other 
types  of  connective  tissue  may  also  be  encountered  in  varying 
amounts  in  the  more  highly  mixed  cancers.] 

TJic  cvternal  shape  and  other  macroscopic  characters  of  cancer 
vary  with  the  location  of  the  original  growth,  the  structural  con- 
stituents of  the  tumor  and  the  age  of  the  neoplasm.  Cancers  de- 
veloping on  the  free  surfaces  of  the  skin  and  mucous  membranes 
[squamous  epitheliomata,  surface  adenocarcinomata^  often  appear 
as  cancerous  ulcers.  The  infiltrative  growth  causes  a  thickening 
of  the  membrane,  with  the  [ulcerated]  exposed  surface  uneven 
with  nodular  prominences,  suppurating,  red  or  dirty  dark  brown, 
and  perhaps  covered  with  crusts,  with  the  base  and  wall  shown 
in  cross  sections  as  a  more  or  less  defined  growth  and  as  a  light 
gray  bacony  zone  often  penetrating  by  root-like  extensions  into  the 
deeper  tissue.  The  normal  epiderm  is  usually  sharply  defined  along 
the  border  of  the  ulcerating  exposed  tumor  surface.  In  mucous 
membranes,  as  the  urinary  bladder,  cancer  often  forms  merely  super- 
ficial, undulating,  slightly  elevated  thickenings  [flat  tabular  swell- 
ings], recognizable  from  simple  inflammatory  changes  by  the 
accompanying  enlargement  of  the  lymph  glands,  the  infiltration  of 
the  growth  into  the  muscular  layers  and  by  the  definition  of  the 


Cancer. 


411 


Sfravish-white  medullarv  tumor  tissue  sccu  in  cross  sec- 
tion.  Of  course  the  microscope  affords  the  coiichisive  diagnosis. 
These    surface    cancers    may    also    develop    into    cauliflower    forms 


Fig.    126. 
Cancer   of  gum    (squamous   epithelioma)    of  liorse. 

(carviol),  masses  of  a  light  gray  to  more  reddish  hue,  growing 
from  the  surface  of  the  skin  or  mucous  membrane,  the  surface  sub- 
divided and  overlaid  by  a  suppurating,  ichorous,  pulpy  mass  of  dis- 
integrating cancer  tissue. 


412  Tumors. 

In  the  interior  organs  cancers  form  nodes  of  widely  varying 
dimensions,  sometimes  sharply  circumscribed  and  rounded,  or  with 
their  tissue  gradually  merging  by  infiltrative  extension  with  that 
of  the  synchronously  enlarging  organ.  The  whole  organ,  as  a 
kidney,  may  be  incorporated  into  the  tumor  tissue,  and  in  its  stead  a 
shapeless  mass  of  cancer  is  met  weighing  perhaps  from  one  to 
fifteen  kilograms.  The  tendency  to  perforate  to  the  surface  of  the 
involved  orgfan  is  a  marked  characteristic  of  cancers.  Another 
peculiar  feature  is  the  production  of  cancer  umbilication,  seen 
rather  irregularly  in  the  smaller  nodes  [secondary  nodes]  about 
to  perforate  through  serous  surfaces ;  it  is  a  central  depression 
seen  in  these  nodes  due  to  the  prominence  of  the  marginal 
growth  and  destruction  of  the  interior  of  the  node.  On  section 
of  cancers  a  milky  fluid  or  juice,  briefly  known  as  "cancer  milk," 
may  frequently  be  obtained  by  scraping  the  cut  surface  or  may  be 
expressed  in  drops  by  compression  with  the  fingers ;  upon  micro- 
scopic examination  it  is  apparently  almost  entirely  composed  of  the 
epithelial  cells  (with  fatty  degenerative  changes)  of  which  the 
cancer  is  constructed. 

The  secretion  of  mucus  and  of  colloid  substance,  as  seen  in 
adenocarcinomata  of  mucous  membranes  and  follicular  glands 
(ovary,  thyroid)  and  the  retention  of  these  materials  in  the  tumor 
tissue  sometimes  gives  an  unusual  softness  and  transparency  to  the 
cancerous  growth,  the  name  gelatinous  cancer  being  often  used  in 
connection  with  such  examples.  [The  term  colloid  cancer  has,  from 
confusion, 'been  employed  indiscriminately  in  these  cases.  Colloid 
cancer,  using  the  term  in  its  strict  sense,  is  practically  confined  to 
the  thyroid  gland,  and  even  there  much  of  the  gelatinous  material 
contained  in  it  is  not  definitely  colloid,  but  rather  mucoid.  The 
use  of  the  term  colloid  for  these  gelatinous  cancers  in  other  situa- 
tions of  the  body  (stomach,  intestine,  ovary,  etc.)  is  almost  sure 
to  be  wrong;  the  change  really  being  a  collection  of  some  type 
of  mucin  within  the  epithelial  cells  and  perhaps  also  in  the  tissue. 
The  cells  which  in  older  text  books  are  described  as  "colloid  seal- 
ring  cells"  are  really  nothing  but  mucoid  goblet  cells,  quite  like  those 
found  in  a  catarrhal  mucous  surface,  but  modified  by  pressure  so  as 
to  have  a  rounded  shape,  flie  mucin  in  their  interior  pressing  the 
nucleus  and  a  part  of  the  cytoplasm  to  one  side  so  as  to  form  the 
prominence  compared  to  the  seal  of  a  ring.]  On  the  other 
hand  some  cancers  come  to  be  very  dense  and  cicatricial  in  consist- 
ence in  case  the  associated  growth  of  their  connective  tissue  should 
be  unusually  marked  in  quantity,  jn  density  of  fibrillation  and  in- 


Cancer.  413 

durative.  The  epithelial  elements  in  such  examples  may  become 
very  unimportant  structural  factors;  these  hard  specimens  arc 
known  by  the  names  scirrhus.  scirrlious  cancer. 

According  to  statistics  compiled  by  Casper,  Frohner  and  Sticker, 
cancers    [among  animals]    are  most   frequent  among  dogs    (three 
per    cent.)  ;    horses    rank    next    in    order,    and    after    them    cats. 
Just  as  in  man  cancer  in  animals  is  a  disease  developing  principally 
in  middle  and  later  life.     This  is  probably  the  reason  for  the  in- 
frequence  of  these  tumors  in  cattle,  sheep,  goats  and  swine,  such 
animals  not  attaining  an  advanced  age  because  of  their  use  for  meat 
supplv.     The  skin  and  its  junctions  wdth  the  mucous  membranes 
are  the  most  frequent  seat  of  growth  [for  squamous  epitheliomata] , 
anal    cancer    in    the    dog   and    cancer    of    the    glans    penis,    gums 
and  lips   in  the  horse  being  frequently  met  with.     The  mammary 
glands  and  thyroid  gland  of  the  dog  are  comparatively   frequent 
points  of  primary  involvement  [adenocarcinoma  or  carcinoma  sim- 
plex  according  to  the   degree   of   atypical   structure   to  which   the 
growth  is  advanced]. 

In  human  beings  cancer  of  the  stomach  and  of  the  female  uro- 
genital organs  constitute  a  high  proportion  of  these  growths;  in 
animals  these  organs  are  afifected  by  cancer  to  a  far  less  degree.* 
As  far  as  the  rest  of  the  body  is  concerned  it  may  be  said  that  pri- 
marv  cancer  has  been  observed  in  all  the  epithelial  organs.  In 
structures  which  do  not  possess  epithelial  cells  (lymphglands,  mar- 
row, spleen,  muscles,  etc.)  cancer  can  occur  only  in  metastases  (in 
rare  exceptions  also  from  embryonal  germinal  misplacements). 
Such  metastatic  growths  sometimes  become  of  greater  bulk  than 
the  primary  tumor,  especially  those  of  lymph  glands. f 

The  general  peculiarities  of  cancerous  growths,  their  irrepressi- 
ble penetration  into  the  tissues  in  every  direction,  the  difficulty  of 
thorough  operative  removal  of  all  their  roots  which  is  only  occa- 
sionally successful  in  the  early  stages  of  the  cancer  and  if  incom- 
'  pletely  accomplished  invariably  results  in  recurrence,  the  destruc- 
tion of  the  affected  organ  and  the  certainty  of  metastasis,  stamp  these 
tumors  as  highly  malignant  autoblastomata.  In  the  course  of  the 
cancerous  affection,  the  severity  of  which  is  determined  by  the  rap- 
iditv  of  dissemination  and  the  location  of  the  growth  and  the  impor- 
tance of  the  tissue  involved,  there  usually  develops  a  condition  of 

*  For  details  see  esp-cially  the  statistics  of  Sticker,  ArcJiiv.  f.  Kliiiisch.  Chir- 
itrgie,  Bd.   6.5,   Berlin,   1901'. 

t  If  the  primarv  growth  has  been  removed  by  operation  and  this  fact  be 
nnknown  to  the  examiner,  or  if  the  scar  at  the  affected  place  be  oyorlookech  the 
secondary  formations  mav   give  the  erroneous  impression   of  being  primary   tumors. 


414  Tumors. 

general  emaciation,  anaemia  and  bodily  weakness,  known  as  can- 
cerous cachexia,  due  at  least  in  part  to  the  reaction  upon  the 
system  by  toxic  products  formed  in  the  cancerous  tissue. 

[The  cachexia  of  cancer  is  of  course  induced  the  more  early  and 
markedly  in  case  the  cancer  involve  some  of  the  organs  of  nutri- 
tional importance  to  the- animal,  as  the  alimentary  tube  or  pancreas; 
the  faults  of  nutrition  being  important  contributors  to  the  produc- 
tion of  oligaemia  and  loss  of  flesh  and  strength.  The  idea  of  toxic 
factors,  although  usually  not  urged  by  writers  because  of  our  ig- 
norance, is,  however,  probably  an  important  one,  these  toxines  aris- 
ing from  the  secretory  activity  of  the  tumor  tissue  or  as  products 
of  tissue  metabolism  or  destruction.  The  metastatic  tendency,  in- 
volving the  progressive  affection  of  more  and  more  of  the  body  by 
cancerous  foci,  must  of  course  be  an  important  factor  of  malig- 
nance. The  occurrence  of  metastases  varies  greatly  with  the  type 
of  the  tumor  and  with  the  definite  resistive  power  which  the  body 
exerts  against  these  practically  parasitic  cells,  this  resistance  being 
apparently  not  at  all  uniformly  possessed  by  the  various  organic 
systems  or  by  different  individuals.  In  a  general  way  it  may  be 
said  that  the  squamous  epitheliomata  are  likely  to  disseminate  more 
slowly  than  the  other  varieties,  progressing  more  regularly  by  a  con- 
tinuous invasion  of  the  lymph  spaces  and  channels,  and  therefore 
showing  a  greater  tendency  to  local  and  neighboring  infiltration  and 
node  production.  Distant  metastases  are  to  be  met  with  but  are  not 
as  frequent  as  in  the  cylindrical  cell  and  glandular  cell  cancers.  Of 
the  latter  groups  in  a  rough  way,  to  which  exceptions  are  common, 
it  may  be  said  that  those  that  manifest  in  their  structure  the  great- 
est departure  from  the  tubular  and  acinous  types  (carcinoma  sim- 
plex) are  those  showing  the  more  rapid  and  extensive  metastatic 
tendency ;  the  adenocarcinomatous  forms  the  less.  Both  are,  how- 
ever, more  apt  to  give  distant  metastasis  than  the  squamous  cell 
form.  The  condition  of  the  stroma  makes  a  difference  as  well,  the 
soft  medullary  types  with  a  small  amount  of  stroma  being  more 
metastatic  and  the  hard  scirrhous  varieties  tending  to  remain  local 
for  a  longer  period.  It  is  said  that  cancers  as  a  group  are  char- 
acteristically generalized  by  way  of  the  lymphatic  system,  in  contrast 
to  sarcomata  which  are  more  frequently  conveyed  by  the  blood  cur- 
rent. This  is,  in  the  main,  true,  and  the  usual  rule  is  to  find  the 
lymph  glands  into  which  the  lymph  drainage  of  the  cancerous  part 
passes  the  seat  of  secondary  cancers.  Yet  it  is  by  no  mean?  neces- 
sarv.     The  route  of  metastasis  and  in  a  great  measure  the  tendency 


Epithelial  Cysts.  415 

to  give  rise  to  metastasis  are  explicable    on    meclianical    grounds. 
The  cells  of  squamous  epitheliomata  are  usually  large  cells  and  are 
less  easily  displaced  from  their  site  of  formation  than  many  of  the 
smaller  cells  of  the  cylindrical  cell  and  glandular  types  of  cancers ; 
and  as  a  group  all  epithelial  cells  are  larger  and  less  easily  dis- 
placed than  the  small  round  cells  of  small  round  cell  sarcoma.   These 
last  mentioned  growths  have  cells  comparable  to  the  small  lympho- 
cytes which  are  always  and  readily  passing  with  the  blood  through- 
out its  entire  capillary  system.     It  amounts  therefore  to  the  general 
rule  that,  whatever  tumor  cells  may  be  able  to  gain  entrance  to  some 
small  capillary  blood  vessels  in  the  tissue  in  which  they  are  growing, 
the  sarcoma  cells  have  a  better  chance  of  convection  than  do  the 
epithelial  cells.    On  the  other  hand  sarcomas  in  their  growth,  direct- 
ly from  and  in  the  connective  tissue  structures  in  which  the  blood- 
vessels are  distributed,  are  more  favorably  situated  as  early  tumors 
to  gain  access  to  these  vessels  than  are  the  epithelial  cells,  which 
primarily  are  separated  from  the  blood  stream  not  alone  by  the  ves- 
sel walls  but  by  more  or  less  connective  tissue  and  by  remnants,  at 
least,  of  a  membrana  propria.     In  their  mode  of  growth  cancers 
primarily  are  more  likely  to  gain  entrance  to  the  lymph  spaces  an  1 
channels,  and  are  therefore  from  the  first  more  favorably  situated 
to  follow  this  system  provided  the  spaces  and  channels  are  of  suf- 
ficient calibre  to  allow  the  convection  of  the  epithelial  cells  (as  they 
usually  are,  in  comparison  with  the  minute  blood  capillaries).     Yet 
granting  such  factors  as  these,  as  determining  the  usual  course  and 
occurrence  of  metastasis,  exceptions  must  arise  and  are  constant'y 
being  seen.     If  a  sarcoma  grow  in  lymphatic  tissue   (a  lymphosar- 
coma for  example)   it  is  very  likely,  whatever  the  size  of  its  cells, 
to  follow  the  lymph  current  to  the  neighboring  nodes;  and  if  in 
some  situation    (as  in  stomach  or  intestinal  wall  where  the  larger 
radicles  of  the  portal  vein  are  close  to  the  cancerous  growth  start- 
ing  in   the   mucosa)    the   cancer  cells   be   afforded   easy   access   to 
bloodvessels  of  sufficient  calibre  to  accommodate  their  size  they  wiU 
be  found  to  give  rise  to  hsematogenous  metastasis    (as  the  portal 
convection  of  gastric  cancer  to  the  liver).] 

Epithelial   Cysts,   Dermoid   Cysts,   Odontomata,   Mixed   Teratomata. 

There  are  a  number  of  tumor-like  formations  which,  as  hollow 
epithelial  lined  sacs,  limited  to  their  place  of  development,  originate 
from  embryonic  cellular  misplacements.  These  are  cysts  (  v  kv<ttis. 
vesicle)   which    arc    not    jiroduccd    from    mature    glandular  organs 


41 6  Tumors. 

fmm  simple  retention  of  their  contents  and  dilatation  of  their 
canals  and  are  not  formed  in  the  loose  structures  of  the  body  from 
exudation  into  them  or  from  liquefaction  of  the  tissues  themselves, 
but  take  their  inception  in  early  embryonic  life  from  displaced  and 
isolated  portions  of  organs,  organic  rests  and  hollow  ofifshoots  of 
such  structures,  and  acquire  an  independence  of  growth. 

The  simplest  type  of  these  cysts  is  the  epidermoid  cystoma  or 
epithelioma  cysticum,  a  sac  of  the  size  of  a  nut,  a  hen's  egg  or  even 
of  a  fist,  which  is  completely  filled  with  loosened  squamous  epider- 
mal cells  almost  all  in  a  keratous  condition;  sometimes  cholesterin 
is  found  mixed  in  with  these.  Bonnet  met  a  genuine  example  of  this 
type  in  the  cranial  cavity  of  a  horse.  All  these  cysts  containing 
squamous  epithelium  doubtless  originate  from  ectodermal  cellular 
inclusions  in  foetal  life,  conceivable  as  occurring  from  friction  of  the 
skin  by  amniotic  strands.  Their  occurrence  in  the  cranial  vault,  near 
the  aural  and  temporal  region,  suggests  that  displaced  portions  of 
the  epithelium  of  the  branchial  arches  constituted  their  original  sub- 
stance, and  in  case  of  those  developing  in  the  brain,  from  the  med- 
ullar}- folds,  the  ectoderm  must  certainly  play  a  part  in  their 
origin.  Experimental  studies  by  Schweninger,  E.  Kaufmann  and 
Ribbert  show  that  epithelial  cysts  can  be  readily  produced  artifi- 
cially by  insertion  of  a  bit  of  epiderm,  conjunctiva  or  tracheal  mu- 
cous membrane  into  the  peritoneum  or  under  the  skin.  When  the 
epithelial  cells  are  supported  by  a  little  connective  tissue  to  preserve 
their  nutrition  they  grow  over  the  interior  surfaces  of  the  wound 
with  which  they  have  been  placed  in  contact,  and  form  the  lining  of 
the  hollow  space,  the  latter  being  occupied  by  the  wound  secretions 
and  desquamated  epithelium.  Epithelial  lined  cysts  may  also  be 
produced,  as  pointed  out  by  these  authors,  by  suturing  over  a  cir- 
cumscribed bit  of  epiderm  the  adjacent  loosened  borders  of  skin; 
the  bit  of  epiderm  beneath  the  sutured  parts  grows  and  fills  in  the 
space  beneath  the  elevated  cutis  (Ribbert).  In  man  as  the  result  of 
accidental  misplacement  of  epithelium  in  operations,  or  of  cutaneous 
lacerations,  similar  cyst  formations  are  well  known  to  occur.  Such 
results  are  known  as  traumatic  epithelial  cysts. 

As  derivatives  of  the  skin  in  its  entirety,  of  the  cutis  with  its 
glands,  of  hairs  and  epiderm,  may  be  mentioned  the  dermoid  cysts 
or  hair  follicle  tumors  (dermatocystis  congenita  or  cystoma  der- 
moides),  which  occur  comparatively  frequently  in  cattle  and  horses, 
situated  in  the  subcutaneous  connective  tissue.  They  appear  from 
the  exterior  as  flat  cutaneous  swellings  or  may  be  found  acci- 
dentally in  skinning  or  eating  beef.     The  cyst  varies  from  the  size 


* 


Dermoid  Cysts.  417 

of  a  nut  to  tliat  of  a  fist,  is  rounded  and  liUcd  with  a  hunch  of 
tang-led  hair  and  a  (hrt\  l)ro\vn  fluid  consisting  of  secretion  fnjui 
the  sweat-glands,  fat  and  desquamated  epithelial  cells.  The  wall 
of  the  sac.  which  may  be  easily  shelled  out  of  its  bed,  is  thin,  quite 
like  the  iibrous  structure  of  the  cutis,  and  lined  on  the  inside 
with  cpiderm  and  attached  hairs,  loosened  hairs  occurring  in  the 
contents  as  free  bunches.  .Microscopically  the  wall  has  all  the 
appearances  of  the  cutaneous  structure.  These  dermoid  cysts  are 
met  particularly  in  the  region  of  the  neck  and  jaw,  generally 
developing  in  these  situations  from  tissue  derived  from  the 
branchial  arches  (braj!chi(\Q:ciioiis  cysts)  ;  they  are  also  met  about 
the  shoulder  or  elbows,  in  which  cases  they  may  be  referred  to 
faults  in  the  development  of  the  anterior  liml)  bud  (Leisering. 
Johne.  Grams  and  others),  in  the  umbilical  region,  and  in  the 
testicles  and  ovaries. 

As  earlv  as  1854  Remak  explained  the  origin  of  dermoid  cysts 
bv  conceiving  an  al)normal  development  of  the  arches  and  resultant 
enclosure  of  a  bit  of  the  germinal  epidermal  layer  as  their  basis ; 
and  it  mav  also  be  possible  that  injuries  caused  to  the  skin  in  the 
region  of  fissures  may  give  rise  to  them,  provided  the  borders  of 
the  fissures  become  the  seat  of  a  cicatrizing  proliferation  and. 
further,  provided  the  base  of  the  skin  fissure  becomes  isolated  and 
brought  to  lie  underneath  the  scar. 

The  dermoid  cysts  of  birds  contain  feathers  ( fcalhcr-folliclc 
cysts,  cxstonia  pcuuifcruni  )  and  are  found  from  the  size  of  an  egg 
to  that  of  a  fist  within  the  abdominal  cavity  of  geese.  UK^re  rarelv  in 
ducks  and  chickens.  The  cyst,  surrounded  by  a  thick  layer  of  fat, 
is  sometimes  free  in  the  ])eritoneum  or  may  l)e  attached  by  a  peri- 
toneal fold  to  the  ovary  and  lumbar  region.  The  number  of  feath- 
ers (the  plume  not  unfolded  because  wet  with  fluid)  may  reach 
several  hundred. 

Analogous  to  tlie  dermoid  cyst  but  not  growing  in  cystic  form,  and 
appearing  as  protruding  islands  of  hairy  skin,  are  the  dermoid  fcratoinata 
of  the  cornea  (also  of  palpcbra  tcrtia).  which  are  met  comparatively  com- 
monly in  cattle  and  dogs.  They  are  congenital  anomalies  and  originate 
from  a  misplacement  or  transplantation  in  the  formation  of  the  palpebral 
fissure. 

In  the  same  way  as  from  the  epidcrm  and  cutis  cystic  foci  ma_\- 
arise  from  separation  or  misplacement  of  their  cells,  epithelial 
lined  cysts  may  also  develop  from  the  mucous  membrane 
tubules  and  glandular  ducts  in  embryonic  life  from  budding  or 
other    anomalies   of   development,   particularly   from    "rests"   of 


4i8 


Tumors. 


gland  tissue  (adenocystoma).  These  entodermal  cysts  are  lined 
by  columnar  epithelium,  sometimes  ciliated,  and  in  man  are  found 
in  the  liver,  intestine  or  peritoneum,  in  the  neighborhood  of  the 
trachea  and  bronchi,  and  in  the  neck,  var\ing-  in  size  from  that 
of  a  pin-head  to  that  of  an  adult  human  head.  In  animals  they 
most  usually  arise  from  rests  of  the  original  urinary  structures, 


Fig.   127. 
Cystic  kidney  of  hog   (section). 

the  Miillerian  or  AVolffian  ducts,  and  are  found  as  transparent 
vesicles  of  the  size  of  a  millet  seed  or  pea  or  sometimes  larger, 
along  the  broad  ligaments  of  the  uterus,  in  the  fimbriae  of  the 
oviduct,  and  in  the  epididymis.  The  congenital  cysts  of  the 
ovary,  occurring  as  single  or  multilocular  and  closely  packed 
cysts  of  this  organ,  and  containing  a  thin  mucoid  and  sometimes 
bloody  material,  are  further  examples  of  the  same  type.  Con- 
genital cysts  of  the  kidney  are  also  regarded  as  results  of  devel- 
opmental disturbances,  converting  the  kidneys,  usually  bilater- 
ally, into  a  grape-like  mass  of  vesicles  with  watery  contents, 
between  which  an  inconspicuous  amount  of  parenchyma  is  found 
reduced  mainly  to  thin  connective  tissue  septa  (cystic  kidneys, 
vesiculated  kidneys).  This  anomaly  is  supposed  to  be  due  to  a 
failure  of  union  between  the  uriniferous  tubules  and  the  develop- 
ing glomeruli,  these  two  parts  growing  separately  (Ribbert). 
The  term  odontoma  and  odontohlastoma  are  applied  to  mon- 


Odontoma. 


419 


strous  tooth-formations,  which  arise  from  faults  in  the  embry- 
onic development  of  dental  suijstanccs  and  present  themselves 
either  as  excrescences  on  the  teeth,  of  bone-like  hardness  and 
composed  of  cement  and  dentine,  or  as  abnormities  in  which  an 
entire  tooth  has  been  changed  into  a  shapeless,  nodular  form 
with  enlargement;  or  in  which  in  combination  with  an  accom- 
panving  proliferation  of  the  soft  connective  tissues  a  compound 
dental  tumor  has  been  produced.  These  neoplasms  arc  always 
congenital,  either  becoming  apparent  at  the  time  of  the  eruption  of 
the  tooth  or  the  teeth  fail  to  erupt  and  a  tumor  slowly  develops 
in  the  alveolar  portion  of  the  jaw  beneath  the  gum,  bulging  the 
latter  and  expanding  the  bone  as  it  enlarges  within  the  alveolus. 
The  composition  and  form  of  these  odon- 
toblastomata  var}'  considerabl\-  with  the 
part  taken  by  the  different  tissues  con- 
cerned in  embryonic  tooth  formation,  the 
dentine  and  its  covering  of  enamel,  the  den- 
tal sac  and  the  peripheral  alveolar  bone. 
The  simple  odontoma  durum,  now  and 
then  seen  on  single  teeth  in  the  cow  and 
horse,  occurs  as  a  mass  about  the  size  of 
a  nut,  rounded,  hard  as  bone,  and  usually 
surrounding  the  crown  or  niore  rarely  the 
root  of  the  tooth.  In  other  instances,  as 
observed  by  \Xe6\  and  ^^lagitot.  the  whole 
tooth  lying  within  the  alveolar  process  is 
changed  into  a  mass  of  bony  hardness  as 
large  as  an  orange  or  possibly  weigh- 
ing   as    much  as   a  kilogram.     The   name 

odontoma  mi.vfum  is  applied  to  a  growth  composed  partly  of 
fibrous  tissue,  bloodvessels,  odontoblasts  and  agglomerated  tooth 
papilL-e,  with  the  hard  parts  in  rudimentary  unshaped  masses  of 
dentine  and  enamel  over  the  surface  or  mixed  in  the  interior. 
Sutton  has  met  with  a  mixed  growth  of  this  type  weighing  seven 
hundred  grams  in  a  horse.  Similar  tumors,  sometimes  only 
enclosing  in  their  structure  a  single  hard  rudiment  of  a  tooth,  or 
sometimes  containing  a  number,  possibly  several  dozen,  mis- 
shapen or  fairly  well  formed  teeth,  occur  as  cysts  or  bunches 
of  cysts,  completely  included  by  fibrogelatinous  dental  sacs  and 
alveolar  bone  capsules  (odontocystoma  capsulars  cystoma  dcnti- 
fcrum  alveolare).  In  other  instances  the  proliferation  of  the 
bony  capsule  is  especially  marked,  surrounding  the  dental  sac- 


Fig.    128. 

Odontoma   of   incisor   tooth 
of  cow    (natural  size). 


420 


Tumors. 


cular  tumor  and  the  deformed  tooth,  and  giving-  rise  to  the  type 
known  as  osteocystoma  capsiilare  dcntifernm.  Occasionally  in 
young  horses  at  the  base  of  the  ear  over  the  temporal  bone  cysts 
may  be  found  which  contain  one  or  several  imperfect  teeth, 
usually  opening  by  a  fistulous  sinus  upon  the  skin ;  these  are 
blind  tubular  invaginations  from  the  skin,  lined  with  mucous 
membrane  and  provided  with  a  bony  covering  or  with  small 
bone  platelets  in  simulation  of  the  alveolar  process  of  the  jaw; 
they    originate   from    the   branchial    arches    and    are    known    as 


Fig.    129^ 
Odontocyst   of  lower  jaw   of  cow. 


Fig.    130. 
Osteocystoma    dentiferum    of    liorse. 


branchiogenoiis  dental  foUicidar  cysts  {odonto-temtoma  bran- 
chiale,  odontocystis  braiichiogcnetica).'^  This  type  of  cysts  is 
only  rarely  met  in  other  animals;  Siedamgrotzky  encountered 
two  dental  cysts  in  the  ethmoidal  turbinate  in  a  hog;  Verwey  has 
recorded  one  in  the  petrous  portion  of  the  temporal  bone  in 
a  dog;  Hertwig  met  a  dental  cyst  in  an  ox. 

Teeth  are  sometimes  found  in  dermoid  cysts  and  teratomata 
in  other  parts  of  the  body,  especially  in  this  type  of  growth  in 

*  For  fuller  description  v.   Kitt,   Lehrbuch  der  pathol,  AnatonUe  der  Haustieve, 
Stuttgart,  F.   Euke's  Verl.     II   Aufl.,   1901. 


Doiti^crous  Cysts.  421 

the  ovary  and  testicle  [heterotopic  odontoteratomata).  Gurlt 
recorded  a  testicular  tumor  of  a  horse,  about  the  size  of  a  fist, 
of  stony  hardness,  containing  six  molar  teeth  (three  separate, 
three  merged  together),  together  with  thin  plates  of  bone  repre- 
senting a  rudimentary  alveolar  process,  and  a  fibrous  capsule; 
in  a  second  instance  the  egg-sized  tumor  contained,  besides  a 
single  tooth,  a  lot  of  hair  and  a  fiuid  material  made  up  of  a 
mixture  of  perspiratory  and  sebaceous  material. 

In  addition  to  the  above  cysts  and  dentigerous  tumors  there 
occur,  especially  in  the  sexual  glands  of  both  sexes,  a  number 
of  other  tumors  of  complex  composition,  sometimes  showing  an 
irregular  mixture  of  heterogeneous  tissues  of  all  three  embryo- 
blastic  layers,  sometimes  a  definite  tissue  arrangement  repre- 
senting clearly  the  structure  of  a  number  of  organs.  Because  of 
their  close  relation  to  monsters  the  collective  names  teratoma  or 
emhrxoma  are  used  in  connection  with  these  peculiar  formations, 
which  undoubtedly  originate  from  embryonal  cells  or  tissues 
which  have  been  segregated  and  become  independent  at  an  early 
developmental   period. 

The  external  tumors  of  this  type,  growing  in  the  superficial 
tegumental    tissue    or    in    the    mouth,    are    possibly   the    results    of 
partial    cleavage    from    amniotic    threads,    as    it    is    known    that 
indentation   of  an   embryonic  tissue   can  cause   its  division   and 
double  development;  and  even  transplantation  may  be  effected 
from  injuries  caused  by  amniotic  bands.     These  external  tera- 
tomata  usually   appear  as  tumor-like,  pedunculated  formations, 
of  lobulated   outline,   and   are   composed   of  hairy   skin,    rudimen- 
tary jaws  with  teeth  and  mucous  memlDrane  covering,  fat  tissue, 
nerves,  muscle  and  glandular  structures.     (For  illustrations  and 
details    v.    E.    Sigl,    Monatshcft    f.    pr.    Tierheilknnde,     Stuttgart. 
1902.)     The  compound  teratomata  developing  in  t}ie  interior  of 
the    body,    especially    in    the    ovary    and    testicle,    may    sometimes 
originate   from   germinal   segregations    from   the    primitive   seg- 
ments of  the  vertebral  column  or  from  the  indifferent  cells  of  the 
Wolffian  body;  or  it  is   possible,  as  Marchand's   theory  would 
make  plausible,  that  they  may  arise  from  the  separate  develop- 
ment  of   one   segmentation   cell.      According  to   the   experimental 
studies  of  Roux  and  others  each  one  of  the  primitive  segmenta- 
tion products  of  the  ovum— that  is,  each  segmentation  cell— is 
capable    of   producing    an    entire    embryo;    thus    the    possibility 
arises    that    an    isolated  segmentation  cell  in  course  of  progressive 
development  may   form  a  group  of  embryonic  tissues,  which  be- 


422  Tumors. 

cause  of  irregular  nutrition  succeed  in  their  later  growth  in 
forming  only  an  amorphous  body  of  all  sorts  of  organic  struc- 
tures mixed  together.  This,  it  is  likely,  enclosed  within  the  indi- 
vidual formed  from  the  other  segmentation  cells,  remains  without 
further  development,  as  a  tumor.  []\Iany  of  the  so-called  ovarian 
dermoid  cysts  met  in  human  beings  are  properly  of  this  last 
type,  complex  teratomata,  frequently  containing  tissues  evidently 
from  two  or  all  three  of  the  embryoblastic  layers.  It  has  been 
suggested  in  addition  to  the  above  explanations  for  such  terato- 
mata in  the  sexual  organs  that  they  may  be  the  result  of  seg- 
mentation and  development  of  an  unfertilized  ovum  directly 
within  the  ovary,  a  parthenogenetic  development.  This  idea  has 
no  wide  acceptance,  but  it  should  be  recalled  that  partheno- 
genetic development  is  well  known  in  many  lower  forms  of  life, 
and  that  Jacques  Loeb  has  succeeded  in  causing  the  development 
of  unfertilized  ova  of  sea-urchins  by  chemical  stimulation.  It 
should  be  added  moreover  that  L.  Loeb  (Archir.  f.  uiikrosk. 
Anat.  It.  Eutzi'icklungsgeschicht.  Bd.  65,  1905)  has  demonstrated 
kar3'okinetic  changes  and  segmentation  of  the  ovum  in  the  ovary 
of  the  unfertilized  guinea-pig.  The  theoretical  possibility  of  this 
mode  of  origin  of  ovarian  teratomata  should  therefore  be  accepted ; 
although  evidence  of  its  actual  prevalence  is  not  clear.] 


FUNCTIONAL    ABNORMALITIES 

Nervous  Disturbances — Disturbances   of  Motion. 

The  nervous  system  regulates  the  functions  of  the  organs  and 
is  the  intermediary  between  the  corporeal  and  psychical  func- 
tions of  the  polycellular  animal  organism.  The  nervous  matter 
may  be  excited  by  both  external  and  internal  agencies  (stimuli), 
and  being  thus  stimulated  gives  to  the  tissues  the  impulse  for 
the  manifestation  of  the  powers  peculiar  to  them.  Alterations 
in  the  excitability  of  the  nervous  system  and  abnormal  stimuli 
which  occasion  such  variations,  may  result  in  functional  dis- 
turbances of  the  nervous  apparatus  and  the  organs  dependent 
upon  it.  Where  the  whole  central  system  is  altered,  these  dis- 
turbances are  general  and  may  manifest  themselves  in  the  widest 
possible  range  (general  nervous  syinptojns)  of  abnormal  nerv- 
ous phenomena  (sensory,  motor,  secretory,  reflex).  Where 
definite  localities  in  the  central  nervous  system  are  subjected 
to  injury,  we  speak  of  central  local  involveynent  and  focal  symp- 
toms. In  this  connection,  too,  nuclear  involvement  where  the 
nucleus  is  affected,  is  differentiated  from  supra-nuclear  in- 
volvement, where  the  course  of  the  conduction  within  the 
central  system — that  is.  above  the  level  of  the  nucleus — is 
the  part  disturbed;  and  according  as  the  focus  affected  lies 
within  the  brain,  in  the  medulla  oblongata  or  in  the  spinal  cord 
the  lesion  is  said  to  be  cerebral,  bulbar  or  spinal.  Where  a 
nerve  is  injured  in  its  course  beyond  its  point  of  exit  from  the 
brain  or  spinal  cord  to  it's  area  of  distribution  or  wdthin  the 
latter,  peripheral  aft'ections  ensue. 

General  Nervous  Disturbances. — The  brain  and  medulla  to- 
gether constitute  the  central  organ  presiding  over  the  whole 
category  of  functional  activities,  and  therefore  everything  which 
causes  depression  or  excitation  of  cerebral  activity  must  of  nec- 
essity bring  about  a  great  variety  and  general  distribution  of 
disturbances.     Every  lesion  of  the  deeper  centres  of  the  medulla 


424  Xei'Z'oits  Distitrbaiices. 

oblongata,  in  which  the  circulatory  and  respiratory  regulative 
apparatus  are  located,  must  necessarily  inhibit  or  depress  these 
most  vitally  important  functions  and  thus  threaten  life.  Lesions 
of  the  cerebral  cortex  bring  about  varying  grades  of  disturbance 
of  consciousness,  which,  including  all  phases  of  mentality,  may  be 
collectivel}'  spoken  of  as  psychical  disturbances. 

The  most  severe  of  the  ps}-chic  paralyses  is  cerebrospinal 
cuiicnssioii  {commotio  cerebri  et  meduUcc).  After  more  or  less 
severe  concussion  of  the  head  or  the  whole  body  by  a  fall,  blow 
()r  kick,  the  functions  of  the  brain  and  cord  cease.  Anatomically 
there  is  often  nothing  to  be  found  in  such  a  case,  beyond  slight 
luemorrhagic  effusions  upon  the  membranes  and  the  skull,  and 
gross  lesions  of  the  nervous  structures  are  absent.  The  severe 
symptom  complex  can  only  be  explained  by  supposing  that 
through  the  influence  of  the  concussion  waves  upon  the  exceed- 
ingl\-  complicated  mechanism  of  the  nervous  system  (compres- 
sion alternating  with  stretching  force)  minute  structural  changes 
nuist  be  induced,  as  destruction  of  the  delicate  dendrites  of  the 
nerve  cells   (Krehl). 

Cessation  of  the  cerebral  function  is  manifested  by  complete 
loss  of  consciousness,  loss  of  all  voluntary  muscular  motility, 
loss  of  pupillary  reactions,  weak  pulse  and  coolness  of  the  exter- 
nal surface ;  and  tends  usually,  in  a  few  minutes,  hours  or  days 
to  death.  In  other  and  milder  instances  only  a  transient  loss  of 
sensibility  occurs.  When  the  cord  is  the  main  part  involved  by  the 
concussion  there  are  met  paralysis  of  the  extremities,  loss  of  sensa- 
tion in  the  latter  and  in  the  trunk,  and  disturbances  of  respiration, 
as  the  principal  symptoms.  Sudden  and  usually  brief  disturb- 
ance of  equilibrium  and  inability  to  maintain  an  upright  posture 
(dizziness,  I'erti'i^o),  associated  with  loss  of  consciousness  (faint, 
syncope),  occur  from  disturbance  of  the  blood  circulation  in  the 
cerebral  cortex  and  in  the  cerebellum  ;  they  niay  result  too  from 
trivial  grades  of  general  anjemia  of  the  brain,  as  a  decrease  in 
the  arterial  supply,  and  also  occur  in  passive  congestion  (cardiac 
disease,  compression  of  jugular  veins)  or  from  anatomical 
changes  of  the  cerebellum,  aural  disease  and  toxic  influences. 
In  uncomplicated  loss  of  consciousness  the  cerebral  cortex  is 
alone  the  seat  of  involvement ;  the  animal  suddenly  begins  to  go 
slowly,  stops  for  a  moment,  staggefs,  leans  against  the  shafts 
or  other  support,  turns  around  in  a  circle  and  falls  ;  then,  after 
remaining  motionless  for  a  few  minutes,  attempts  with  labored 
movements  of  the  limbs  to  get  up.  and  is  gradually  able  to  rise  and 


Psychic  Disturbances.  4^5 

resume  consciousness.    Sometimes  vomiting  (in  dogs)  and  invol- 
untary discharge  of  urine  and  feces  ensue. 

(For    details    see     Friedberger-Frohner,     Veterinary    Pathology,    Amer. 
Ed.,   1904.     W.  T.  Keener  &  Co.,  Chicago.) 

Persistent     unconsciousness,     coma    {to  KWfxa,     lethargy,      from 
KOiixdw,     to  hill  to  sleep),  or  sopor  {sopor,  a  sleeping  draught),  is  a 
state    of    insensibility    which    is    met    in    serious    brain    afifections, 
intoxications     (uremia)     and     particularly     in     connection     with 
haemorrhages    from    the    cerebral    vessels;    in    the    last    when    it 
occurs  suddenly  and  paralysis  results,  the  process  is  usually  called 
a     brain     or     nerrous     stroke      (apoplexia     cercbralis,     nervosa: 
dKOTr\-n<raeiu,      to  Strike  down).    When  unconsciousness  occurs   par- 
oxysmally,  accompanied  by  muscular  spasms    and    loss    of    sensa- 
tion it  is  known  as  falling  sickness  or  epilepsy  {  v  iTrlXvi^i^  )  ;  it  de- 
pends   ui)on   some   functional    disturbance   of   the   cortical   centres, 
the  real  cause  of  which  is,  however,  unknown.     Compression  of 
the  intracranial  structures,  as  from  blood  clots,  tumors,  increased 
pressure    of    the    cerebro-spinal    fluid,    or    collections    of    exudate, 
give    rise    to    the    symptoms  of    compression   of  the  brain   (brain 
depression).     These  consist  of  general   dulHng  of  the  senses,  a 
somnolent,   lethargic   attitude,    staggering   and   awkward   gait   and 
diminution   of  sensibility.     The   animal   stands  as  though   deaf, 
leans  against  some  adjacent  body  for  support,  hangs  its  head  or 
supports  it  against  the  wall  or  manger,  and  the  eyelids  are  closed 
as  if  in  sleep  and  the  pupils  dilated.    The  animal  may  be  hard  to 
move  from  one  spot  and  may  continue  for  hours  at  a  time  in  some 
abnormal  posture   (legs  crossed  or  kneeling),  or  may  run  about 
with  staggering  gait  into  the   wall  and  all  sorts  of  obstacles,   or 
may   continually   move   about   in   a   ring;    it   is   apathetic   when 
spoken  to.  touched,  whipped,  bitten    by    flies,  etc.;    takes  no  food, 
or  holds  its  food  in  the  mouth  without  chewing,  pushes  its  nose 
deep  into  the  water  in  drinking;  and   may  show  other   special 
pressure  symptoms  according  to  the  particular  part  of  the  brain 
•   affected    (reversed   movements,   riding  paces,   focal   movements, 
dancing  or  rolling  movements,  or  pressing  toward  one  side).     In 
the  man  and  the  dog  there  are  also  observed  peculiar  alterations 
of    the     eye-ground,     so-called     [choke     disc]     papillary     conges- 
tion   (really    a    papillitis,    inflammation    of   the    papilla    and    optic 
"nerve);     in     horses    with     blind     staggers     these    are     not     noted 
(merely    an    ansemia    recognized — Friedberger-Frohner).      These 
symptoms   depend  upon   the  fact  that  in   the  first  place  in  the 


426  Nervous  Disturbances. 

conditions  indicated  disturbances  of  the  blood  circulation  arise, 
as  compresison  of  the  large  veins  before  opening  into  the  rigid 
walled  sinuses,  with  resultant  stasis,  interference  with  the  escape 
of  venous  blood  and  cerebro-spinal  fluid,  and  the  production  of 
increased  pressure  upon  the  brain  substance ;  that,  further,  in 
the  conditions  mentioned  increased  formation  of  this  fluid  and 
special  tissue  changes  in  the  brain  may  obtain,  and  perhaps,  too, 
toxic  influences   (bacterial  toxines^  autotoxines). 

Psychical  excitement  has  its  causative  factors  in  hypersemia 
of  the  brain,  cerebral  inflammatory  changes,  heat  or  toxic  influ- 
ences, and  occurs  in  a  number  of  difl^erent  degrees  of  severity. 
The  main  symptoms  are  manifested  as  attacks  of  insanity 
{mania,  delirium  fnribundum).  The  animals  in  these  attacks 
suddenl}^  lose  their  docility,  try  to  free  themselves  from  their 
fastenings,  bite  their  owm  bodies,  make  attacks  in  whatever  way 
is  natural  to  them  (strike  out,  kick,  try  to  bite),  run  into  obstacles 
and  violently  knock  them  over,  stand  up  on  their  hind  legs  and 
throw  themselves  about  with  shrill  cries,  grit  their  teeth  and 
froth  at  the  mouth  ;  the  eyes  become  staring  and  wild,  the  con- 
junctivae injected;  and  finally  the  animals  collapse  and  go  into 
spasms  and  convulsions.  Especially  in  dogs  of  usually  aitec- 
tionate  and  lively  disposition,  well-trained  and  possessed  of 
special  intelligence  we  meet  with  the  widest  range  of  mental 
disturbances,  from  melancholia  to  hallucinations  (fancied  per- 
ceptions), marked  confusion  and  insane  outbursts,  as  in  rabies 
(depressed  stupid  condition,  snapping  at  the  air,  purposeless 
wandering  about,  sudden  attacks  of  desire  to  bite,  tearing  of  the 
animal's  own  flesh),  or  in  poisoning  with  deadly  night-shade  or  in 
sunstroke.  Similar  symptoms  of  excitement  are  seen  in  dogs 
in  the  autointoxication  produced  by  the  portal  blood,  that  is,  the 
absorbed  products  of  albuminous  decomposition  in  the  intes- 
tine, in  Eck's  fistula  [fistula  made  between  the  portal  vein  and 
vena  cava  with  diversion  of  the  portal  blood  from  the  liver]. 
Special  nervous  excitement  and  reflex  psychic  conditions  occur 
in  some  of  the  diseases  of  the  genital  organs  (ovarian  cysts, 
ovarian  tuberculosis,  uterine  affections,  undescended  testicle), 
the  ' affected  animals  manifesting  (uterine,  ovarian,  orchitic 
psychoses)  an  exaggerated  sexual  desire  (nymphomania,  satyriasis, 
erotomania,  rutting,  sexual  insanity). 

There  are,  too,  a  number  of  vague  nervous  conditions  which 
l^ad  to  perversions  of  taste    (perversions  of  appetite)    manifested 


Psychic  Distuyhauccs ;  Motor  Disturbances.  427 

in  animals,  especiall}-  by  the  group  of  symptoms  known  as 
''licking"  or  pica  (wool-eating  sheep),  the  animals  showing 
an  inexpressible  desire  to  lick  all  sorts  of  objects,  even  nauseat- 
ing substances,  and  to  eat  them ;  an  ultimately  fatal  cachexia 
developing  in  the  chronic  forms  of  these  morbid  appetites. 
[Analogous  to  the  pica  of  chlorosis  and  other  anaemias  in  man, 
and  the  dirt-eating  habit  of  the  an?emic  hosts  of  uncinaria ; 
probably  many  cases  in  animals  are  really  expressions  of  a  simi- 
lar parasitism.]  In  rabid  dogs  there  is  a  strong  tendency  to 
swallow  foreign  bodies.  In  sows  the  habit  of  eating  the  pigs  and 
in  ruminants  of  devouring  the  placenta  are  expressions  of  psychic 
abnormalities. 

(For     fuller     details     see     Friedberger-Frohner,     Veterinary    Patliology, 
Amer.  Ed.,  1904.     W.  T.  Keener  &  Co.,  Chicago.) 

Motor  Disturbances. — Aluscular  movements  are  normally — 
I,  Voluntary,  stimulated  by  the  psycho-motor  elements  of  the 
gray  cortical  substance  of  the  brain;  2.  automatic,  caused  by  chem- 
ical stimuli,  independently  of  voluntary  influence,  occurring 
rhythmically  and  at  all  times  present;  3.  reflex,  performed 
unconsciously  and  caused  by  transmission  of  sensory  excitation 
to  the  motor  apparatus;  4,  co-ordinated  and  combined,  the  rapid 
succession  and  repetition  of  voluntary  and  involuntary  move- 
ments as  group  actions,  represented  by  facility  of  movement 
acquired  from  practice  (Samuel).  Disturbances  of  movement 
(motility)  depend  either  upon  pathological  changes  f'n  the  mus- 
cles, tendons,  bones  and  joints,  or  upon  changes  in  the  motor 
nerves.  The  motor  tract  begins  in  the  large  ganglionic  cells  of 
the  central  convolutions,  passes  by  the  long  pyramidal  fibres  to 
the  cells  of  the  anterior  horns  of  the  spinal  cord  and  thence  pass 
peripherally  by  the  nerves  distributed  to  the  muscles.  In  addition 
those  fibres  and  cells  of  the  cerebral  cortex  which  are  concerned  in 
perception,  ideation  and  volitional  stimulation  are  more  or  less  in- 
volved in  the  production  of  voluntary  movements.  The  complicated 
and  widely  distributed  tract  may  be  exposed  at  any  point  in  its 
entire  length  to  influences  which  are  capable  of  interfering  with 
its  functions.  Such  disturbances  manifest  themselves  either  as 
pathological  exaggeration  or  pathological  impairment  of  motility. 

Pathological  exaggeration  of  motility  is  manifested  by  spasms; 
spasm  or  hyperkincsis  (17  Kii>r)<ns)  may  be  defined  as  a  paroxysmal 
muscular  contraction  which  is  occasioned  by  pathological  stimu- 
lation or  which,  if  caused  by  ordinary  stimuli,  exceeds  normal 


428  Xerz'oits  Disturbances. 

degrees  of  contraction.  A\'hen  the  members  of  the  body  are 
thrown  into  motion  by  these  contractions  alternating  with  relaxa- 
tion the  spasm  is  said  to  be  clonic  (6  kUvos  ,  violent  movement)  or 
alternating;  when  the  contraction  persists  for  a  longer  time, 
causing  maintenance  of  rigidity  in  one  position,  it  is  said  to  be 
tonic  (0  TOfos.  tension).  Tonus  and  clonus  may  succeed  each 
other  alternately.  The  mildest  form  of  spasm  is  tremor,  really 
a  quick  succession  of  contractions  of  single  muscles  or  muscle 
groups,  the  coarser  types  evident  as  visible  and  palpable  jerkings. 
These  muscular  contractions  or  spasms  are  spoken  of  as  convul- 
sions when  they  give  rise  to  excessive  movement  of  the  body 
and  limbs,  or  violent  tremors  of  the  whole  body  (Samuel).  Tonic 
spasm  of  individual  muscles  or  of  only  one  group  of  muscles  is 
also  termed  a  cramp  (as  of  the  jaw-muscles,  trismus,  from  rpl^ui, 
to  grit)  :  the  powerful  and  long  continued  contractions  of  the 
greater  part  of  the  musculature,  tetanus  (  reivu,  to  strain)  ;  a 
general  body  rigidity,  without  any  important  contraction  (merely 
the  ordinary  contraction  to  maintain  position),  catalepsy;  long- 
continued  shortening  of  individual  groups  of  muscles,  with  perma- 
ment  deformity  as  a  consequence,  contracture  (distinguished  as 
active,  spastic  or  reflcxophile  in  distinction  from  the  passive  con- 
tractures not  of  nervous  origin  met  in  disease  of  joints).  Convul- 
sions when  accompanied  by  loss  of  consciousness  are  described 
as  epileptic  or  epileptiform. 

We  know  in  connection  with  the  causes  of  spasms  that  they 
may  be  induced  by  a  group  of  poisons  or  chemical  irritants 
(tetanotoxine,  strychnine,  ergotin,  lead,  carbonic  acid  gas),  and 
may  be  produced  by  poisonous  substances  arising  as  metabolic 
products  in  the  body  (in  uraemia),  and  that  muscular  contrac- 
tions may  result  (directly  or  reflexly)  from  mechanical  excitation 
(section,  torsion,  crushing).  In  certain  instances  the  spasms 
are  caused  by  local  lesions  of  the  peripheral  nerves,  of  the  cord 
or  of  the  brain  (focal  lesions),  as  the  convulsions  of  suffocation 
by  lack  of  oxygen  supplied  to  the  medulla  oblongata,  those  of 
tetanus  by  the  chemical  combination  of  the  toxine  with  the 
nervous  substance  of  the  spinal  cord.  The  more  minute  lesions 
which  take  place  in  such  examples  are  as  yet  not  known,  and  the 
extremely  confused  ideas  we  possess  of  the  relations  between 
processes  of  excitation  and  inhibition  prevent,  for  the  present, 
any  satisfactory  explanation  of  the  conditions  involved. 

The  results  of  spasms  vary  with  the  location  of  the  causa- 
tive influence  in  the  svstem.     When  the  cause  is  directlv  in  the 


Mot<)r  nishirbditccs. 


429 


muscles  the  cfifccts  of  the  spasms  arc  of  little  importance,  except 
that  in  kmg;  standin^^  contracture  atrophy  is  likely  to  develop. 
Spasm  of  the  respiratory  muscles  of  necessity  causes  fatal  suffo- 
cation because  of  interference  willi  respiratory  movements. 
Spasms  of  the  muscles  of  mastication  cause  starvation.  In  other 
examples  a  fatal  termination  may  be  explained  by  the  primary  or 
some  collateral  action  exerted  by  the  poisons  causing'  the  con- 
vulsions, the  tetanus  poison  for  example  acting  both  by  the 
lesions  induced  in  the  ganglionic  cells  and  by  a  hemolytic  action. 
It  should  be  kept  in  mind  that  th.e  spasms  themselves  are  noth- 
ing more  than  the  symptoms  of  the  actual  nervous  disturbances. 

(For    details   v.    Friedberger-Fr(")lincr,    Lchrbucli    tier    klinischcn    fJiilcr- 
siichifiii^siiicfliodcii   f.    Ticrarztc.   III.   Aufl.   Stuttgart.     F.    Enke.) 

Loss  of  muscular  power  is  termed  [^als\  (akiiicsis  [a.  prii'.,] 
TyKij/T/o-is,  nv)vement )  and  may  be  differentiated  into  a  complete  loss  of 
mobility  (paralysis) ,  or  ])artial  loss  {paresis)  in  which  the  power 
of  the  muscles  to  perform  movements  is  only  reduced  in  degree. 
In  case  of  deficiency  in  co-ordination,  where  the  movements  are 
performed  clumsily  and  hesitatingly,  the  term  ataxia  ( a  priv., 
ij  Td^ts,  arrangement )  is  employed.  Loss  of  motion  occurs  in 
pathological  changes  which  directly  inhibit  muscular  contractility 
(atrophy,  inflanuuation,  rupture,  degenerations),  or  interfere  with 
the  movements  of  the  bones  (ankylosis  of  joints),  or  in  conditions 
of  inefificient  innervation  which  induce  palsy  both  indirectly  by 
reducing  the  stimulus  for  contraction  and  by  causing  local 
changes   [in  the  muscle]. 

A  faulty  innervation  itself  is  usuall}'  the  result  of  anatomical 
changes  involving  the  ganglionic  cells  or  nerve  fibres  and  thus 
interfering  with  the  formation  of  impulses  or  interrupting  their 
transmission,  as  for  example  stretching^,  disintegration  of  the 
nervous  substance  by  pressure  (tumors),  or  destruction  and  degen- 
eration from  poisons  (toxines,  lead),  or  disturbances  of  blood  sup- 
ply. The  location  of  the  changes  may  be  in  the  central  motor, 
apparatus,  cerebral  cortex  or  cord  (cerebral  or  spinal  palsy),  or 
in  the   nerve   trunks  and   their   terminations    (peripheral   palsy). 

The  central  and  some  of  the  peripheral  palsies  are  usually 
unilateral  (hemiplegia)  because  they  are  'usually  due  to  focal 
lesions,  to  local  changes,  in  one  of  the  bilaterally  i^laced  nerve 
ganglia  or  nerves;  wdiile  spinal  palsies  generally  involve  both 
sides  of  tlie  body  (paraplegia)  because  in  the  comparatively  small 
transverse  area  of  the  spinal  cord  the  lesion  causing  the  anatomical 


430 


Nervous  Disturbances. 


changes  is  apt  to  occupy  the  whole  extent  of  the  transverse  section 
{transverse  spinal  palsy). 

Inhibition  of  the  motor  centres  may  also  be  caused  by  exces- 
sive stimulation  of  the  sensory  nerves  in  a  reflex  manner  (so- 
called  reflex  paralysis  or  neurolytic  palsy),  as  where  complete 
paralysis  of  the  posteripr  part  of  the  body  occurs  after  forcible 
compression  of  the  kidney,  bladder,  ureter  or  a  portion  of  the 
bowel  (Samuel). 

Results  and  terminations  of  palsies.  The  results  of  motor  loss 
vary  with   the  duration,   extent  of  disturbance,  the   importance 


Fig.   131. 

Paralysis  of  ttie  posterior  part  of  the  body  :  transverse  spinal  palsy.      (Photograph 

by   D:-.   Jakob.) 

of  the  affected  muscles  and  of  the  causative  lesion.  In  paralysis 
of  the  heart  and  respiratory  muscles  death  at  once  ensues  from 
cessation  of  circulation  and  gas  interchange.  Indirectly  palsies 
of  the  pharyngeal  muscles,  the  bladder,  the  intestine  or  the 
extremities  may  result  in  death  because  of  the  development  of 
various  possible  complications  (aspiration  of  fluid  in  the  air 
passages  causing  aspiration  pneumonia ;  retention  of  urine  and 
fecal  material  with  production  of  dilatation,  inflammation  and 
erosion  of  the  mucous  membrane :  hypostases  and  decubitus  with 
blood  poisoning,  etc.).  In  case  of  paresis  of  the  sphincter  of  the 
bladder  the  urine  constantly  dribbles  and  the  same  symptom  con- 


Sensory  Disturbances.  431 

stantly  occurs  with  palsy  of  the  sphincter  and  detrusor  muscles ; 
when  the  detrusor  alone  is  paralyzed  and  the  sphincter  is  intact  the 
urine  collects  in  the  bladder.  Paralyses  due  to  destruction  of 
ganglion  cells  are  irreparable;  but  peripheral  palsies  may  some- 
times recover  by  regeneration  of  nerve  fibres.  When  regenera- 
tion of  nerves  does  not  occur  in  the  spinal  palsies  due  to  destruc- 
tion of  the  gray  matter  and  anterior  nerve  roots,  the  paralyzed 
muscles  undergo  atrophy  and  degeneration,  with  rapid  loss  of 
electrical  irritability.  Tn  case  of  central  palsies  atrophy  does 
not  occur   (Samuel).  * 

Sensory  Disturbances. — The  sensory  nerves  transmit  pres- 
sure and  temperature  sensations,  special  sensations  (smell, 
taste,  sight,  hearing),  and  the  so-called  general  sensations 
(hunger,  thirst,  special  cutaneous  sensations,  sense  of  position). 
It  is  assumed  that  just  as  for  the  special  senses  there  are  par- 
ticular nerves,  there  are  also  for  every  other  sort  of  sensation 
special  nerves;  and  it  is  knov/n  that  nerves  sensitive  to  pres- 
sure, pain,  cold  and  heat  have  entirely  specialized  and  character- 
istic endings  (v.  Frey,  Krehl).  From  these  local  receptive  end- 
organs  the  sensation  is  conveyed  ccntripetally  to  the  perceptive 
psycho-sensory  parts  of  the  brain,  where  proper  distribution  is 
made  to  the  tracts  and  innumerable  connections  occur  with  the 
reflex  and  automatic  nerves  and  ganglia.  Disturbances  of  sensation 
may  be  considered  as  of  two  types,  pathological  excitation  and 
pathological  depression  of  sensation.  Pathological  excitation  of 
sensory  nerves  gives  rise  to  symptoms  of  sensory  irritation  of 
the  most  varied  forms  and  grades,  according  to  the  kind  and 
position  of  the  terminal  organ  and  the  lesions.  Sensation  of 
pain  is  caused  by  stimulation  of  the  nerves  of  pain,  which  are 
distributed  in  profusion  and  have  their  terminations  in  the  skin, 
at  the  mucous  membrane  orifices,  serous  and  synovial  mem- 
branes; these  peripheral  parts  of  the  body  therefore  being  capable 
of  manifesting  the  most  severe  attacks  , of  pain.  Mechanical, 
chemical  and  thermic  stimuli  induce  this  symptom.  If  the 
nerve  be  in  a  condition  of  exaggerated  irritability  (hyperces- 
thesia)  ordinary  physiological  variations  (muscular  action,  ten- 
sion of  tissue,  congestion)  are  sufficient  to  bring  on  pain.  Cer- 
tain forms  of  pain  apparently  develop  spontaneously  (nenralgia), 
that  is,  without  demonstrable  anatomical  lesions  and  from  unknown 
changes.  The  tracts  extending  from  the  muscles,  bones  and 
glands  and  into  the  central  nervous  system  are  less  sensitive  to 
pain;   although   painful    symptoms   may   be    noticed    arising    from 


432 


Xerz'oiis  Disturbances. 


sach  locations  also,  as  in  affections  of  the  spinal  cord.  In  the 
brain,  as  indicated  by  the  absence  of  pain  during  operative  pro- 
cedures, the  sensibility  to  pain  is  very  low,  at  least  in  the  cortical 
areas.  Only  hairs,  hoof,  and  cartilage,  provided  the  matrix  be 
not  also  involved,  are  entirely  devoid  of  the  sense  of  pain,  be- 
cause of  the  absence  of  nerves  from  these  structures. 

The  existence  of  pain  is  shown  in  animals  partly  by  general 
symptoms  (restlessness,  pawing,  stamping,  running  about,  roll- 
ing over,  groaning,  sighing,  gritting  the  teeth,  whining  and  cry- 
ing shrilly),  partly  by  local  symptoms  which  suggest  and  more 
or  less  clearly  indicate  the  location  of  the  painful  trouble 
(scratching,  hobbling,  protective  movements  when  touched,  strik- 
ing against  the  abdomen,  looking  around  toward  the  posterior 
part  of  the  body,  arching  of  the  back,  symptoms  of  colic). 

Itching,  indicated  by  the  tendency  to  scratch,  is  met  in  cuta- 
neous aft'ections,  in  some  intoxications  and  general  disturbances : 
it  must  be  due  to  an  irritation  of  the  nerve  endings  (pressure 
points,  Krehl),  but  the  mode  of  origin  is  unknown. 

The  irritative  symptoms,  ''formication,"  "going  to  sleep"  of 
some  part,  which  are  caused  by  pressure  upon  nerve  trunks 
iparcrsthcsia),  light  and  color  phenomena  from  irritation  in  the 
optic  tract  (pJiotopsia,  chrotnopsia),  abnormal  temperature  sen- 
sations, cannot  be  determined  in  animals,  as  they  are  subjective 
perceptions. 

Pathological  di^niniition  of  sensation.  Tn  lesions  which  inter- 
rupt the  course  of  the  nerves  at  any  position  or  render  function- 
less  the  parts  subjected  to  irritation,  sensation  is  entirely  lost 
or  diminished  or  its  transmission  slowed.  Sensory  palsy  (anccs- 
thesia)  may  be  induced  by  traumatic  destruction  of  continuity 
(nerve  section,  crushing),  by  freezing,  cauterizing  the  endings, 
by  local  anaemia,  oedema,  degeneration  or  atrophy  of  the  peripheral 
nerves  or  brain  and  cord  segments,  as  well  as  by  the  local  and 
general  action  of  certain  medicaments  (anodynes  and  anaes- 
thetics, as  morphine,  chloroform,  ether,  chloral  hydrate).  Paraly- 
sis of  sensation  may  be  total,  so  that  practically  every  kind  of  sen- 
sation is  lost :  or  it  may  be  partial,  as  when  the  sense  of  pain  is 
abolished  and  the  pressure  sense  or  sensitiveness  to  electrical  irri- 
tation is  retained,  or  where  the  special  senses  are  destroyed  but  the 
sense  of  pain  is  intact. 

The  results  of  disturbed  sensation  depend  upon  the  impor- 
tance  of  the   physiological    functions   abolished.     Anaesthesias    of 


Sensory  I)is!iirbaiiccs.  433 

the  optic  system  cause  visual  weakness  (amblyopia)  or  com- 
plete blindness  (aiiuuirosis) .  Auccsthesias  of  the  auditory  nerves 
produce  nervous  difficulty  of  hearing-  (hy/'iicusis)  or  com- 
plete deafness  (aiiaciisis).  Loss  of  the  sensory  jiower  of  peri])h- 
eral  nerves  is  sometimes  a  source  of  danger  for  the  tissues 
(for  "the  senses  are  the  guardians  of  health"),  which  become 
conscious  of  every  injury  from  the  stimulus  of  pain  and  arc  tlius 
able  to  call  into  action  every  protective  means  and  measure  the 
body  possesses.  '  In  ansesthesia  of  the  conjunctiva  the  entrance 
of  foreign  bodies  to  the  eye  or  conjunctival  sac  is  not  rcali;-ed,  and 
such  substances  are  not  carried  off  b\-  the  How  of  tc;irs.  After 
section  of  the  sensory  nerves  of  the  foot,  penetration  of  a  nail  into 
the  frog-  is  not  evinced  by  lameness,  and  the  ensuing  inflannna- 
tion  and  gangrene  of  the  hoof  proceed  unnoticed — conditions  of 
serious  consequence  to  the  life  of  the  subject.  Interruption 
of  the  sensory  portion  of  the  reflex  arc  puts  an  end  to  the  tendon 
reflexes,  which  cease  in  anaesthesia  of  the  peripheral  nerves  because 
the  path  of  conduction  to  the  reflex  centre  (pyramids)  is  broken. 
If.  however,  the  latter  be  intact  and  the  communication  between 
the  brain  and  ganglion  be  destroyed  the  tendon  rcHexes  are  ex- 
aggerated  (central  inhibition  may  also  exist).     (Krehl.) 

Loss  of  the  so-called  motor  senses  destroys  the  coordination  of 
movements  and  causes  the  appearance  of  synijitoms  of  vertigo  (v.  p. 
424).  The  sense  of  station  of  the  limbs,  which  renders  i)ossible  the 
acts  of  walking,  standing  and  especially  of  orientation  in  sjiacc. 
depends  upon  coordination  of  the  optic  and  auditory  organs,  and 
especially  those  portions  of  the  latter  enclosed  in  the  i)etrous  ])or- 
tion  of  the  temporal  bone,  as  well  as  of  the  centripetal  sensations 
from  the  muscles,  tendons,  bones,  joints,   fasciae  and  skin. 

Where  there  is  loss  of  a  single  sense,  as  that  of  sight.  orientatitMi 
mav  be  possible  from  increased  acuteness  of  other  senses  (tactile 
sense,  hearing)  up  to  a  certain  degree  Loss  of  sensory  muscle  im- 
pulses or  deficient  transmission  of  these  impulses  or  anaesthesia 
of  the  cerebral  or  spinal  centres  cause  more  or  less  loss  of  power 
of  bodily  motion.  Disturbances  of  equilibration  of  the  body  occur 
especially  in  diseases  of  the  organs  in  the  semicircular  canals,  in  the 
saccule  and  utricle,  as  well  as  of  the  central  communications  of  these 
structures  with  the  cerebellum.  How  far  in  these  instances  we  have 
to  deal  with  a  pathological  stimulation  or  pai-al\sis.  whether  there 
exist  a  destructive  phenomenon  or  one  caused  1)\-  deficient  transmis- 
sion  of   imi)ulses,   are   (luestious   difficult   to  decide  l)eeause    of     the 


434  Nervous  Disturbances. 

complexity  of  the  nervous  mechanism  and  even  more  because  of  the 
great  variety  of  processes  and  causes  possible  in  case  of  such  dii^- 
turbances. 

Trophic,  vasomotor  and  secretory  disturbances  depending  upon 
nervous  influences. — Of  the  vast  number  of  cells  which  make  up  the 
animal  body,  there  are,  it  is  true,  some  cells,  which  are  independent 
of  the  nervous  system,  acquiring  their  nutrition  and  performing 
their  function  by  means  of  their  own  parenchyma  alone.  These  are 
the  isolated  blood  cells  and  lymph  cells.  All  the  other  cells  and  tis- 
sues, however,  in  the  matter  of  their  metabolism,  growth  and  main- 
tenance of  existence,  depend  upon  the  nervous  system ;  and  die  if 
they  be  separated  from  it.  The  part  played  by  the  nerves  in  tliis 
connection  is  known  as  the  trophic  influence.  This  is  most  clearly 
apparent  in  nerve  fibres  themselves,  which  invariably  degenerate  if 
divided  from  their  ganglia  or  if  the  latter  be  the  seat  of  disease.  In 
warm-blooded  animals  disintegration  in  the  form  of  fatty  degenera- 
tion sets  in  as  early  as  from  four  to  six  days.  A  nerve  fibre  may 
be  looked  upon  as  the  elongated  process  of  a  ganglion  cell,  and  in 
this  conception  disintegration  is  easily  understood  when  it  is  re- 
called that,  as  taught  by  *Verworn  and  Krehl,  any  part  of  a  cell 
which  has  been  separated  from  its  nucleus  is  sure  to  die.  There  is. 
it  is  true,  a  certain  degree  of  individuality  of  the  different  segments 
of  the  nerve  fibres  so  far  as  concerns  their  nutrition,  metabolism  and 
diseases,  but  permanent  maintenance  of  their  integrity  is  only  as- 
sured by  their  continuity  with  the  ganglion  cells.  And  reversely  the 
central  portions  of  a  neuron  (that  is  to  say,  the  ganglion  cell)  suffer 
if  their  connection  with  the  peripheral  nerves  is  broken ;  for  example, 
after  section  of  a  nerve  atrophy  of  the  central  portion  also  occurs, 
perhaps  extending  to  the  ganglion.  It  is  recognized  that  the  integ- 
rity of  the  ganglia  and  nerves  is  dependent  upon  the  exercise  of 
their  function,  that  functional  stimulation  is  essential  for  mainte- 
nance of  their  nutrition  and  life.  Atrophy  usually  appears  in  the 
voluntary  muscles  as  soon  as  they  lose  the  influence  of  their  proper 
ganglion  cells  in  the  anterior  horns  of  the  cord  or  of  the  equally 
important  cerebral  parts  ;  that  is,  when  these  become  diseased  or  the 
communicating  paths  are  interrupted  or  injured.  The  muscles,  there- 
after incapable  of  voluntary  movements,  are  thus  rendered  immobile 
(inactive,  or  paralyzed),  become  decreased  in  volume  from  diminu- 
tion in  size  of  their  individual  fibres  (simple  atrophy,  atrophy  from 
disease),  or  may  perhaps  undergo  granular  and  fragmentary  disin- 
tegration of  their  contractile  material  (degeneration  atrophy)  ;  a 
rapid  shrinkage  resulting,  arid  transformation  of  the  muscle  into  flat, 


Trophic,  Secretory  and  Vasomotor  Disturbances.  435 

thin  bands  of  fibrous  connective  tissue.  To  what  degree  this 
atrophy  may  be  due  simply  to  the  motor  inactivity  or  is  dependent 
upon  a  loss  of  proper  nutritive  influences  as  the  principal  factor  is 
not  certain.  In  simple  disuse  of  muscles,  as  that  obtaining  in  case 
of  disease  of  the  joints  and  bones  or  artificial  fixation,  atrophy  may 
not  appear  for  a  long  time,  and  the  structure  and  electrical  irrita- 
bility remain  unchanged,  because  the  motionless  muscle  is  still  in 
connection  with  its  unaltered  ganglion  cell,  performs  other  functions 
as  heat  production  and  metabolism,  and  continues  to  receive  impulses 
of  various  kinds.  In  a  neuropathic  paralysis,  however,  the  muscle 
no  longer  receives  stimuli  from  the  nerves  and  its  metabolism  no 
longer  is  as  active;  and  atrophy  may  set  in  as  early  as  within  the 
first  week  after  the  nerve  lesion,  and  may  be  so  marked  that  in  the 
course  of  a  month  tlie  muscle  may  be  reduced  to  half  its  former 
thickness.  From  these  considerations  it  is  evident  that  not  mere 
inactivity  alone,  but  the  loss  of  some  special  trophic  relation  between 
the  nerves  and  muscle,  determine  the  issue. 

The  most  common  example  of  such  neuropathic  atrn]i]iy  is  ^^een 
in  the  shrinkage  of  the  posterior  crico-arytenoid  muscle  in  laryngeal 
hemiplegia  (laryngeal  wheezing  in  the  horse). 

(For  details  v.  Friedberger-Frohner.  Veterinary  Pathology,  Amer.  Ed.. 
W.  T.  Keener  &  Co.,  Chicago;  Dexler,  Die  Ncrvenkrankheiten  des  Pfcrdes, 
1S99   (Denticke's  Verl.)  ;   Thomassen.  Moiiafsheft  f.  praht.     Tierhcilkunde.) 

In  the  same  way  in  case  of  disease  or  loss  of  continuity  of  the 
nerves  nutritional  disturbances  develop  in  the  bones  (rarefaction, 
atrophv),  the  salivary  glands  and  testicles  (diminution  in  size,  de- 
generation of  the  parenchymatous  cells).  The  effect  of  castration 
upon  the  development  of  the  body  and  the  change  of  physical  habit 
is  presumably  also  to  be  attributed  to  some  trophic  influence  of  the 
nervous  system. 

Secretory  disturbances  resulting  from  nervous  lesions  conform 
closely  to  the  known  physiology  of  glandular  activity.  It  is  well 
known  that  by  direct  or  indirect  stimulation  of  the  secretory  nerves 
of  the  salivary  glands  (facial  nerve,  gustatory  nerve,  trigeminus 
and  branch  of  glosso-pharyngeal :  stimulation  by  digitalin,  pilocarpin, 
or  inflammation)  an  increased,  sometimes  permanently  increased, 
secretion  of  saliva  results.  Similarly  a  flow  of  tears  is  induced  by 
stimulation  of  the  lachrymal  nerve,  cervical  sympathetic,  trigeminus, 
and,  too,  reflexly  by  irritation  of  the  nasal  mucous  membrane. 

Vasomotor  disturbances  (angioneuroses)  manifest  themselves  by 
abnormal  dilatation  or  constriction  of  the  vessels,  the  former  deter- 


436  Disturbances  of  Digestion. 

mining  a  hypergemia,  the  latter  an  ansemia  of  the  organ  affected. 
Centres  for  the  vascular  nerves  are  located  in  the  floor  of  the  fourth 
ventricle,  in  the  dorsal  and  lumbar  cord  and  in  the  ganglionic  and 
nervous  plexuses  which  regulate  the  tone  or  ordinary  state  of  con- 
traction of  the  arteries  and  the  dilatation  or  constriction  of  the  ves- 
sels to  any  calibre,  and  which  are  located  about  the  walls  of  the  ves- 
sels themselves.     Stimulation  of  the  fibres  regarded  as  vasoconstric- 
tor causes  diminution  of  calibre,  auc-emia  and  lowered  temperature 
of   the   organ   involved ;   afterwards    passing   into    paralysis,    from 
which  dilatation  results.    Paralysis  of  the  vascular  nervous  centres 
also  induces  dilatation  of  the  vessels  and  rapid  lowering    of    blood 
pressure  (section  of  cord,  paralyzing  poisons).     Stimulation  of  the 
vasodilators  causes  marked   dilatation    of    arteries,   capillaries  and 
veins  and  is  induced  especially  by  local  toxic  influences. 

Disturbances  of  Digestion. 

Diseases  of  the  mouth,  tongue,  jaws  and  teeth  all  interfere  with 
the  taking  of  food  and  with  mastication  as  well  as  the  insalivation 
of  the  food  within  the  mouth.  The  supply  of  nutritive  material  is 
thus  diminished  according  to  the  grade  and  duration  of  such  faults, 
and  conditions  of  failure  of  nutrition  and  starvation  are  brought 
about.  As  the  secretion  of  the  gastric  glands  is  in  reflex  associated 
relation  with  the  movements  of  chewing  so  as  to  insure  the  imme- 
diate bathing  of  the  swallowed  bolus  in  proper  juices  (Pawlow),  it 
is  to  be  expected  that  in  case  of  insufficient  mastication  the  food 
taken  into  the  stomach  will  be  provided  with  a  deficient  amount  of 
gastric  juice  and  will  therefore  of  necessity  remain  a  longer  time 
in  the  stomach. 

The  movements  of  mastication  mechanically  cleanse  the  mouth  of 
its  mucus  and  bacteria  (immediately  after  prolonged  chewing  of 
food  the  mouth  is  almost  aseptic)  ;  anything  which  causes  diminu- 
tion of  these  movements  favors  marked  accumulation  of  micro- 
organisms, as  a  result  of  which  acid  fermentations  take  place  in  the 
mouth,  facilitating  decay  of  the  teeth,  accumulation  of  tartar  on  the 
teeth,  pharyngeal  catarrh,  etc. 

In  various  diseases  of  the  mouth  (as  foot  and  mouth  disease), 
in  a  number  of  toxic  disturbances  (mercurialism)  and  nervous  affec- 
tions (trigeminus),  there  ensues  from  direct  or  indirect  nervous 
irritation  an  increased  flow  of  saliva,  the  secretion  dribbling  from 
the  mouth  (salivation,  ptyalisui).  Dribbling  of  saliva  may  also  be  a 
symptom  of  paralysis  of  the  lips. 


Discuses  of  Pharynx^  (Esophagus  and  Stomach.  437 

Diseases  of  the  pharynx  and  the  adjacent  structures  niav,  on  the 
one  hand,  give  rise  to  faults  of  obtaining  food  (painful  inflamma- 
tions), and  on  the  other  hand  if  swallowing  is  interfered  with  by 
such  conditions  important  complications  may  arise  as  consequences. 
As  the  respiratory  and  alimentary  canals  cross  in  the  pharynx  and 
the  epiglottal  orifice  must  be  closed  in  the  act  of  swallowing  and  the 
nasal  cavity  must  also  be  shut  off  from  the  mouth  by  the  superior 
pharyngeal  wall,  there  arises  a  danger  in  all  affections  which  dimin- 
ish the  contractile  power  of  the  musculature  of  the  pharyngeal  walls 
(peripharyngeal  oedema,  inflammations,  etc.)  that  particles  of  food 
and  saliva  may  And  their  way  into  the  nose  or  into  the  larynx  and 
lungs.  Sometimes  the  food  and  drink  runs  back  (regurgitates)  into 
the  nose,  or  in  case  of  pharyngeal  palsy  remains  in  the  pharynx 
itself ;  and  under  such  circumstances  drops  and  particles  of  the 
pharyngeal  mucus  and  food  may  be  drawn  into  the  respiratory  pas- 
sages (aspirated).  The  fluids  of  the  pharynx  and  mouth  are  apt 
to  contain  great  numbers  of  bacteria,  and  these  foreign  agents  mav 
cause  in  the  lungs  the  most  serious  inflammatory  disturbances,  ter- 
minating in  gangrene  {gangrenous  inhalation  pnciinioiiia) . 

Diseases  of  the  Oesophagus  may  cause  important  interference 
with  nutrition.  Both  by  constrictions  and,  too,  by  patholog- 
ical dilatations  of  the  gullet  the  food  is  prevented  from  passing 
regularlv  into  the  stomach.  The  larger  fragments  lodge  at  the 
place  of  stenosis  and  in  any  dilated  parts,  or  in  case  of  paralysis 
lie  stagnant  in  the  lumen  of  tlie  tube  and  block  the  passage. 
This  induces  retching  movementjs  (antiperistaltic  contractions) 
on  the  part  of  the  cesophageal  musculature,  or  if  the  oesophageal 
muscles  are  paralyzed  vomiting  movements  on  the  part  of  the 
stomach  (pressure  b\'  the  stagnant  mass  and  by  the  oesophagus, 
stuffed  full  like  a  sausage,  upon  the  \agus  nerves).  Further- 
more these  stagnating  masses  of  food  undergo  fermentation, 
cause  injury  to  the  mucous  membrane  and  may  in  this  way  lead 
to  rupture  of  the  oesophagus ;  and  in  the  latter  event,  from 
escape  of  septic  materials,  the  surrounding  tissue  (cellular  tis- 
sue of  neck,  mediastinum  and  thoracic  cavity)  is  apt  to  undergo 
suppuration  and  gangrene.  In  ruminants  from  partial  or  com- 
plete obstruction  of  the  oesophagus  (new  growths,  pressure  from 
enlarged  mediastinal  lymph  nodes)  regurgitation  of  the  gastric 
contents  and  eructation  of  gases  from  the  stomach  are  interfered 
with,  with  tlie  resultant  development  of  clironic  flatulence. 

Diseases  of  the  Stomach. — The    efficiency    of    the    gastric    func- 


438  Disturbances  of  Digestion.  % 

tion  is  disturbed  in  two  ways  in  disease,  the  gastric  secretion  be- 
ing'affected  in  the  first  place  and  in  the  second  the  gastric  motihty 
being  more  or  less  affected.  Usually  both  factors  are  involved 
at  the  same  time,  being  directly  or  indirectly  dependent  upon 
each  other.  Disturbances  of  secretion  are  for  the  most  part 
characterized  by  such  features  as  diminution  of  the  gastric  juice, 
decrease  in  the  proportion  of  acid  (subacidity)  and  of  pepsin 
resulting  from  degeneration  of  the  glandular  epithelium  in  acute 
and  chronic  catarrhs,  anaemia,  etc.,  or  by  continuous  secretion  of 
gastric  juice  without  intervals  ol  rest  (caused  by  local  inflamma- 
tory stimulation  of  the  nerves  of  the  mucous  membrane).  In 
the  latter  condition  the  secretion  is  apt  to  be  poor  in  its  hydro- 
chloric acid  and  peptic  enzyme,  and  its  increased  volume  accounted 
for  by  hypersecretion  of  mucus.  The  secretion  under  such  cir- 
cumstances is  likely  to  be  of  diminished  functional  value,  or  to  be 
entirely  incapable  of  digestive  action,  such  a  condition  being 
termed  dyspepsia.  Although  the  passage  of  tlie  gastric  contents 
into  the  intestine  is  the  principal  -factor  in  preventing  serious 
prevalence  of  bacteria  in  tlie  stomach,  the  acid  of  the  gastric  juice 
has  a  part  in  restricting  the  growth  of  bacteria  and  the  occurrence 
of  putrefactive  changes  in  the  viscus.  A  gastric  juice  poor  in  acid 
must  be  decidedly  diminished  in  its  antiseptic  action,  and  for  this 
reason  a  num.ber  of  types  of  bacteria  grow  luxuriantly  in  the 
stomach  in  dyspeptic  conditions.  The  gastric  contents  are  often, 
in  these  instances,  found  to  be  neutral  or  alkaline  in  reaction,  and 
putrefactive  fermentation  is  present;  where  in  spite  of  deficiency 
of  hydrochloric  acid  an  acid  reaction  prevails  (dyspepsia  acida), 
this  is  due  to  the  formation  of  acetic  acid  (from  alcohol,  yeast 
fermentation)  and  lactic  and  butyric  acids  (from  glucose,  through 
the  activity  of  bacteria). 

In  other  cases  there  may  exist  a  hypersecretion  with  excessive 
hydrochloric  acid  production,  or  the  latter  (hyperacidity)  may 
obtain  without  any  increase  in  the  digestive  fluid  (as  a  result  ol 
special  conditions  of  irritation),  with  the  effect  of  inhibiting  starch 
digestion  and  causing  gastric  pain  and  vomiting  (Krehl). 

The  products  of  fermentation  and  putrefaction  of  the  gastric 
contents  act  as  toxic  irritants  upon  the  mucous  membrane,  and 
may  occasion  further  degenerative  and  inflammatory  changes  in 
that  tissue.  Under  these  and  other  circumstances,  which  induce 
(whether  from  circulatory  disturbances  or  from  the  local  lesions 
and  toxic  influences)    paralysis  or  weakness  of  gastric  peristalsis 


Diseases  of  the  Stomach.  439 

(gastric  atony),  the  churning  and  mixing  of  the  gastric  contents 
with  the  secretion  are  not  thoroughly  accompUshed.  When  the 
ingested  matter  is  thus  inefficiently  dealt  with  the  undigested 
material  is  apt  as  a  result  to  remain  stagnant  in  the  viscus,  and 
this  in  turn  favors  increased  fermentation  and  putrefaction.  As 
gases  are  very  likely  to  be  present  among  the  products  of  these 
processes,  flatulence  of  the  stomach  {meteorisin,  from  nereupi^eiv, 
to  inflate)  may  be  expected,  varying  in  its  intensity  ac- 
cording as  to  whether  the  gas  finds  its  way  through  the  pylorus, 
is  absorbed  or  finds  an  outlet  through  the  gullet  in  belching,  or 
whether  it  fails  to  escape. 

Delay  in  emptying  of  the  stomach  or  retention  of  the  contents 
favors  gastric  dilatation.  A  distended  stomach  because  of  its 
increased  volume  causes  pressure  influtnces  upon  the  adjacent 
parts,  compresses  the  liver,  vena  cava,  etc.,  interferes  with  the 
diaphragmatic  movements  and  thus  renders  respiration  difficult. 
Even  in  moderate  degrees  of  distension  the  absorptive  powers 
of  the  gastric  mucous  membrane  is  dinnnished  because  of  the 
tension  of  the  lymphatics  and  blood  vessels.  The  distended  wall 
of  the  stomach  may  rupture  and  fatal  haemorrhage  from  the  torn 
blood  vessels  quickly  terminate  life.  Digestive  faults  in  the  first 
stomach  of  ruminants  occur  in  the  same  general  way  as  above, 
but  with  the  difference  that  there  is  here  no  secretion  from  the 
gastric  mucous  membrane  and  we  have  to  consider  merely  the 
macerating  properties  of  the  fluid  swallowed,  mixed  with  saliva. 
In  these  animals  accumulation  of  gas  and  tremendous  distension 
invariably  occur,  either  suddenly  or  gradually,  when  the  con- 
tractile power  of  the  wall  of  the  paunch  is  lost.  This  may  be 
caused  by  a  number  of  influences,  as  chilling"  of  the  mucous  sur- 
face of  the  paunch  by  frozen  or  rain-drenched  food,  overfeeding 
or  overwork  without  allowance  of  time  for  rumination,  or  toxic 
substances  capable  of  causing  paresis  of  the  gastric  wall  and  met 
in  various  food  stufifs.  as  lucerne  or  clover.  ^leteorism  may  also 
be  noticed  when  belching  of  gas  is  prevented  by  constrictions  of 
the  oesophagus. 

Exaggerated  gastric  mbvemcnts  occur  especially  in  connection 
with  pyloric  obstruction,  or  from  the  influences  of  chemical  ma- 
terials which  directly  irritate  the  mucous  membrane  of  the  viscus 
or  the  smooth  muscle  of  its  walls,  or  mav  be  caused  indirectlv 
by  influences  acting  on  the  medulla  oblongata  (reflexly  and  by 
irritation  of  the  vagus).     The  violent  contractions  of  the  muscle 


440  Disturbances  of  Digestion. 

of  tlu'  organ  may  ^ause  it  to  be  rapidly  emplied  into  the  intes- 
tine, or.  in  association  with  the  mnscles  of  respiration  (spasmodic 
contraction  of  the  muscles  of  the  abdominal  wall  and  diaphragm), 
may  cause  vomiting  (■z'oiiiitiis) .  It  may  be  safely  assumed  that, 
as  in  man,  more  or  less  gastric  pain  is  caused  also  in  animals  by 
various  affections.  Distension  of  the  stomach,  the  marked  stretch- 
ing of  the  wall,  give  rise. to  a  sense  of  pressure:  and  the  local 
effects  of  poisons,  of  increased  proportions  of  acid,  and  of  toxic 
bacterial  products  upon  the  sensory  nerve  fibres  of  the  mucous 
membrane,  and  especially  the  occurrence  of  spasms  of  the  gastric 
muscles,  must  surely  often  cause  intense  pain.  It  is  known  that 
in  man  migraine  and  vertigo  as  well  as  epileptiform  convulsions 
may  he  of  gastric  origin,*- apparently  from  vagus  irritation;  and 
some  of  the  nervous  symptom  groups,  as  distemper  of  dogs,  may 
perhap>  l:e  expltiined  by  gastric  changes. 

Diseases  of  the  Intestines. — In  all  intestinal  diseases  the 
micru-organisms,  which  teem  in  the  contents  and  cause  all  sorts 
of  disintegrative  changes  in  the  material,  play  an  important  part. 
Bacteria  of  many  t_\pes,  yeasts  and  hyphomycetes,  as  well  as  in- 
fusoria, are  to  l)e  found  in  the  intestine  of  the  healthy  human  be- 
ing and  animal,  being  introduced  with  the  food.  Pasteur  and 
Schottelius  have  pointed  out  that  the  presence  of  these  corn- 
mensualists  is  an  absolute  necessity  for  the  herbiverous  animal, 
the  bacterial  processes  being  adjuvants  in  the  digestion  of  the 
food  ( it  has  been  impossible  to  keep  alive  chicks  hatched  in 
sterile  surroundings  upon  artificially  sterilized  food)  ;  although 
young  guinea  pigs  have  shown  their  alnlitv  to  live  and  thrive  on 
pure  milk  diet  without  bacteria  in  llun-  intestine  (Thierfelder 
and  Xuttal). 

The  harmlessness  of  the  ordinary  intestinal  bacteria  is  due 
to  the  fact  that  the  healthy  epithelium  of  the  gastric  and  intestinal 
mucous  membrane  acts  as  an  impenetrable  barrier  against  them; 
the  protective  means  possessed  by  these  cells  being  apparently 
their  strongly  acid,  albumen  precipitating  nucleinic  acids  (Klem- 
perer).  Again  it  is  possible  that  the  intestinal  epithelium,  as  well 
as  the  rest  of  the  tissue  in  every  indivklual.  may  become  accus- 
tomed to  the  toxic  products  of  the  ordinary  intestinal  bac- 
teria, just  as  the  epithelium  of  the  stomach  and  upper  part 
of  the  intestine  is  acid  proof ;  or  it  may  be  that  an  immunity 
is  obtained  by  the  formation  of  antibodies.  Then  too  the 
acid    gastric    and    small    intestinal    juice,    as     well    as    the    bile, 


Diseases  of  Ihe  J iilestiiies.  441 

surely  possess  sonic  degree  of  influence  inhibiting-  the  multipH- 
cation  of  tlie  inicro])hytes  taken  in  with  tlie  food  Marked  ex- 
cessive prevalenc<^  of  l)acteria  i.^,  however,  niainl\  ])revented  by 
the  comparatively  rapid  passage  of  the  chyme  through  the  small 
intestine  and  the  discharge  of  large  quantities  of  microorganisms 
periodically  with  the  dejecta  from  the  large  bowel  in  regular 
defecation. 

Ir  conditions  which  interfere  with  the  normal  passage  of  the 
chvme  through  the  intestinal  tract,  as  in  stagnation  of  the  intes- 
tinal contents  from  obstruction,  strictures,  etc.,  or  where  the 
epithelium  of  the  mucous  membrane  has  undergone  changes 
(degeneration,  necrosis,  desquamation),  even  the  ordinary  in- 
testinal bacteria  are  capable  of  causing  harm ;  and  this  is  obvi- 
ously possible  where  other  types  of  microphytes  having  special 
toxic  properties  are  introduced,  these  perhaps  causing  epithelial 
necroses  or  their  toxic  products  being  absorbed.  We  should  re- 
gard, at  any  rate,  as  harmful  products  of  ordinary  intestinal 
bacteria  the  products  of  acid  fermentation  of  the  carbohydrates 
(lactic  acid,  butyric  acid,  acetic  acid),  these  when  present  in  large 
amount  causing  erosion  of  the  mucous  membrane  (especially 
the  delicate  mucous  membranes  of  young  individuals),  and  gases, 
as  hydrogen  and  methane  and  sulphuretted  hydrogen,  arising  in 
albumen  putrefaction. 

The  metabolic  products  of  the  bacteria  themselves  are  even 
more  numerous  and  their  influences  varied.  But  little  is  known 
of  their  relation  with  the  pathology  of  the  intestine,  and 
there  is  so  nmch  confusion  as"  to  the  nature  of  these  some- 
times poisonous  su1)stances.  and  their  relation  to  the  alkaloids, 
albuminates,  enzymes,  etc.,  that  it  is  at  present  best  to  be  satis- 
fied with  their  tentative  classification  into  toxines  and  endotoxines. 
We  can  only  speak  in  a  general  way  of  the  bacterial  processes  in 
the  intestinal  canal  as  the  source  of  pathogenic  and  fatal  changes, 
and  say  that  on  the  one  hand  they  occasion  local  lesions  like 
inflammations,  hcemorrhages  or  necroses,  and  on  the  other  hand 
give  rise  to  general  intoxications.  Similar  efifects  may  be  pro- 
duced bv  the  ingestion  of  various  chemical  substances  (poisons 
taken  in  with  the  food).- 

In  many  intestinal  affections  disturbances  of  the  absorptive 
power  of  the  mucous  meiubrane  ensue.  This  is  especially  true 
of  the  diffuse  lesions ;  although  in  circumscribed  changes  the 
intervening   portions    of    mucous    membrane    remaining    unaltered 


442  Dishtrbanccs  of  Digestion. 

continue  to  act  and  to  transmit  as  usual  the  sugar  and  albu- 
men to  the  blood  and  the  fat  to  the  chylous  vessels.  The 
causes  of  impairment  of  absorbent  power  lie  primarily  in  the 
alterations  of  the  intestinal  epithelium,  which  normally  acts 
in  fact  by  attracting  the  nutrient  substance  to  it  (Krehl),  and  in 
the  second  place  in  the  disturbances  in  the  lymph  follicles  of  the 
intestine ;  and,  too,  the  passage  of  the  intestinal  contents  may 
be  too  rapid  to  favor  absorption,  the  period  of  contact  of  the 
nutrient  material  with  the  intestinal  mucous  surface  being 
curtailed.  The  terms  looseness  of  the  bozvels  or  diarrhoea  are 
applied  to  the  accelerated  passage  of  the  chyme  through 
the  intestine,  apparent  from  the  fluid  or  thin  intestinal  dis- 
charges. The  usual  cause  of  this  condition  is  a  heightened  peris- 
taltic action  of  the  intestinal  musculature;  which  may  prevail 
throughout  the  intestinal  tract  or  be  restricted  to  the  large  intes- 
tine, and  is  due  to  irritation  of  the  sensory  nerve  filaments  in 
the  mucous  membrane,  with  transmission  of  the  impulse  to  the 
motor  nerves  of  the  intestinal  muscles.  According  to  Cohnheim 
extensive  and  general  movements  of  the  intestine  can  be  aroused, 
starting  from  any  level  of  the  gastro-intestinal  canal,  by  merely 
moderately  strong  irritation.  Hand  in  hand  with  the  increased 
movement  hypersecretion  from  the  mucous  membrane  may  take 
place,  a  transudation  from  the  blood  vessels,  as  another  effect 
of  local  irritation.  The  irritant  substances  are  of  innumerable 
chemical  types,  including  materials  ingested  from  the  outside  of 
the  body  (drastic  purgatives)  or  decomposition  products  formed 
in  the  bowel  itself.  According!  to  Krehl  the  ocganic  acids  and 
gases  (carbonic  acid,  hydrogen)  are  especially  efficient  in  stim- 
ulating intestinal  movements.  When  the  intestinal  mucous 
membrane  is  already  inflamed  and  hypersemic  even  an  ordinary 
amount  of  irritation  is  sufficient  to  cause  increased  peristalsis,  as 
the  nerves  are  even  then  subjected  to  pressure  from  the  distended 
blood  vessels  and  transudate  (Cohnheim)  or  are  deprived  of 
their  protective  covering  because  of  the  defects  in  the  mucous 
membrane.  Diarrhoeas  may  also  be  caused,  however,  by 
prevention  of  absorption  of  water  from  the  intestine,  which 
may  be  the  case  when  salines  are  present  in  the  gut,  these  sub- 
stances having-  a  strong  tendency  to  combine  with  water  and 
being  themselves  difficult  of  absorption  (saline  laxatives).  Sud- 
den changes  of  the  blood  currents  and  the  blood  gases,  soaking 
or   chilling  the   skin,   or   putrid   blood   poisoning   are   also   factors 


Diseases  of  the  Intestines.  443 

which  directly  or  indirectly  are  liable  to  cause  spasmodic  contrac- 
tions  of   the   intestinal   muscles    (dyspcristalsis). 

As  already  stated  the  absorption  of  nutritive  material  is  dis- 
turbed in  diarrhcEas;  but  in  addition  the  digestive  secretions  and 
the  digestible  constituents  of  the  food  are  carried  out  of  the  body 
by  the  frequent  dejections.  Besides  there  are  losses  of  the 
epithelium  of  the  mucous  membrane,  losses  of  the  inflammatory 
albuminous  transudate  or  of  blood;  so  that  the  body  suffers  also 
a  loss  of  its  circulatory  and  organic  albumens.  For  these  reasons 
diarrhreas  weaken  the  strength  of  the  subject,  bring  about  a 
state  of  inanition  and  may  perhaps  be  fatal.  Although  resorption 
is  reduced  in  diarrhoeas  it  is  not  entirely  checked,  being  main- 
tained in  this  or  that  segment  of  the  bowel;  because  of  this  it  is 
possible,  in  addition  to  the  disturbances  mentioned,  that  re- 
sorption of  toxic  substances  may  prevail,  this  feature  adding 
complications  to  the  morbid  condition  and  aiding  in  bringing 
about  a  fatal  termination. 

There  are  a  variety  of  influences  which  may  retard  the  pas- 
sage of  the  chyme  or  completely  stop  its  movement.  Infrequent 
defecation,  protracted  retention  of  the  chyme  in  the  large  gut, 
obstipation  or  constipation  (constipare,  to  render  compact),  or 
simple  stoppage  of  the  bowel,  is  usually  due  to  the  character  of 
the  food,  which  ma\-  cause  the  chyme  to  be  too  thick  because  of 
insufficient  presence  of  water  or  which  does  not  stimulate  the 
mucous  membrane  enough  and  causes  an  atony  of  the  muscles  of 
the  intestine  (from  feeding  bones  to  dogs,  bran  to  horses).  A 
constriction  or  complete  closure  of  the  intestinal  lumen,  stenosis, 
obturation  or  occlusion,*  may  be  due  to  presence  of  foreign  bodies 
(enteroliths,  concretions,  swallowed  stones,  cork  stoppers,  etc.), 
to  tumors  or  to  cicatrices.  Or  the  intestine  may  be  compressed 
or  squeezed  from  without  {strangnlation  of  intestine,  incarcera- 
tion) when  caught  in  some  opening  (rupture,  hernia),  or  sur- 
rounded by  some  band :  may  be  twisted  {intestinal  tzvist,  volvulus)  ; 
or  become  impermeable  because  one  segment  becomes  invag- 
inated  in  another  (intestinal  intussusception,  invagination).  The 
obstruction  of  the  lumen  in  all  such  cases  causes  a  retention 
of  the  chyme  with  accumulation  toward  the  stomach,  and  the 
possibilitv  of  passage  of  the  intestinal  contents,  both  food  refuse 
and  gases,  to  the  anus  is  interrupted.  The  chyme  stagnating 
abpve  the  obstruction,  in  which  the  processes  of  bacterial  decom- 

*0'bstfucre,  to  barricade,  stop  up  ;  occlvdere,  to  close  up  ;  ohtururc,  to  divert, 
according  to  Roth,  probably  from  9vpa,  door. 


^^_|.  Disturbances  of  Digestion. 

position  are  continually  going  on,  distends  the  intestine,  partic- 
ularly by  gaseous  inflation.  If  the  lumen  is  merely  narrowed  and 
not  completely  obstructed  and  if  the  obstructing  cause  is  slow- 
in  development,  a  compensatory  hypertrophy  of  the  musculature 
mav  ensue  (v.  p.  255),  and  for  a  time  overcome  the  difficulty; 
the  strengthened  wall  by  its  more  forceful  contractions  succeed- 
ing in  forcing  the  tiuid  chyme  through  the  narrowed  passage. 
Where  occlusion  is  sudden  and  complete,  however,  the  retained 
contents  accumulate  in  such  amounts  and  the  gaseous  distension 
becomes  so  intense  that  serious  symptoms  and  results  are  in- 
duced. The  pressure,  whether  from  without  or  from  \\ithin  the 
gut,  upon  the  nerves  of  the  intestinal  wall  and  mucous  membrane 
and  their  irritation  by  the  chemical  substances  in  the  contents, 
cause  violent  contractions,  spasms  of  the  smooth  muscles  ;  which, 
either  by  anti-peristaltic  movements  or  because  of  mere  disten- 
sion of  the  tube,  and  because  from  vagus  irritation  retching 
movements  are  set  up,  induce  overflow  and  regurgitation  of  the 
chyme  into  the  stomach,  a  process  known  as  ileus  (6  d\eb?, 
from  etX^o.,  I  close,  or  dXiw.  I  turn,  according  to  Roth)  or 
niiscrcrc.  l)ecause  of  the  frightful  torture  which  it  causes. 
The  violent  muscular  spasms  of  the  intestine  are  accom- 
panied by  severe  pains,  colicky  pains  or  griping  (i)Kw\iK-n,  sup- 
ply v6sos  ;  from  t6  kwUv,  the  colon),  giving  place  to  an  intestinal 
paralysis  due  to  fatigue  of  the  U'uscular  tissues  and  the  stretch- 
ing of  the  wall  from  gas  accumulation.  The  distension  as  well 
as  the  spasmodic  muscular  contractions  may  lead  to  rupture  of 
the  intestine,  along  with  pressure  upon  the  neighboring  organs 
antl  the  large  blood  vessels  of  the  abdominal  cavity.  The 
stretching  of  the  nerve  fibres  (splanchnic)  with  its  reflex  effect 
upon  the  heart,  the  continuous  vomiting  and  the  absorption  of 
toxic  substances,  make  up  a  group  of  processes  which,  with  rapid 
loss  of  strength,  cause  the  death  of  the  animal.  In  conditions  in 
which  strangulation  of  the  bowel  causes  the  occlusion  there  are 
added  to  the  above  phenomena  disturbances  of  the  blood  cir- 
culation in  the  intestine,  venous  congestion,  congestive  haemor- 
rhages and  transudates,  and  gangrene.  Gangrene  necessarily 
must  result  from  the  penetration  of  the  intestinal  bacteria  into 
the  tissues  which  are  engorged  with  blood,  without  the  least  cir- 
culation and  therefore  necrosing. 

Diseases  of  the  Liver. — The    manifold    functions    of    the    liver 
make  it  easilv  realized  that  any  alTection  of  this  organ  which  is 


Diseases  of  the  Liver.  445 

associated  with  destruction  of  its  secretory  parenchyma  or  with 
disturbances  in  the  entrance  or  exit  of  blood,  should  be  followed 
by  numerous  reactive  efifects  upon  the  general  body.     The  chem- 
ical function  of  the  liver  does  not  extend  merely  to  the  production 
of  bile   and   furnishing  of  glycogen,   but  is   directed  to  the  pro- 
duction of  a  large  number  of  enzymes  having  for  their  purpose 
the    dissolution,    transformation,     precipitation   or     complete     de- 
struction   of   toxic    material    circulating   through    the    blood,    but 
brought    to    the    liver    especially    from    the    intestine.      The    liver 
possesses,    therefore,    an    antitoxic    function,    and    is    a    toxolytic 
organ   of  the   greatest   importance.     According   to   Bangger   and 
Zschokke    the    following    enzymes    have    been    isolated    from    the 
liver  or  bile;   maltase,  glykase,  a  proteolytic   ferment    (similar  to 
trypsin),   nucleinic  ferment,   aldehydase,   Hpase,   fibrin  ferment,   a 
milk  curdling  ferment :  and  there  have  also  been  recognized  a  fer- 
ment  capable   of   forming  ammonium   and  urea   from   the   amido 
acids,   one   forming  glycogen   from   sugar   or   the    reverse   change 
(of    sugar    from   glycogen),    another    forming    iron    and   bilirubin 
from    hemoglobin,    and    finally    one    causing   the    combination    of 
cholic   acid   with  glycocol  and   taurin.   and  of   phenol   with   ethyl- 
sulphuric  acid.     A  large  number  of  alkaloids  are  rendered  com- 
pletely or  partly  inert  by  the  liver.     Schiflf  proved  experimentally 
that  a  dose  of  nicotine,  which  is  fatal  if  injected  into  a  peripheral 
vein,   is   Vv'ithout   effect   if  injected  through   the  portal   vein,   and 
that   an   infusion   of   nicotine   made   into   an   emulsion   with   fresh 
liver   tissue   loses   its   toxic    properties,   while    if   rubbed   up   with 
muscle    or   nervous    tissue    quickly   evinces    its    toxicity.      In    the 
same  way  strychnine,  cicutine.  veratrine,  caffeine,  atropine,  curare 
and    animal    toxines.    extracts    from    putrefied   tissue,    have    been 
found  to  be  less  toxic  if  mixed  with  liver  tissue  or  injected  by 
wav  of  the  portal  vein  so  that  they  must  first  pass  through  the 
liver.     Roger  has   shown  that  the  portal  blood  before  coming  to 
the    liver     contains    a    considerable    amount    of    toxic    substances 
apparently   absorbed   from   the  intestine:   the  blood   of  the   other 
veins  of  the  bodv.  on  the  contrary,  showing  a  far  less  toxic  quality 
in  spite  of  the  fact  ihat  it  carries  with  it  various  metaboHc  prod- 
ucts from  the  tissues.     The  intestine  is  a  chemical  laboratory  in 
which  a  great  quantity  of  bodies  of  the  most  varied  character  are 
formed    from    the    combination    of    the    digestive    juices    with    the 
food:   and   then,   too,   the   myriads   of  bacteria   which   inhabit   the 
intestine   give   origin  to   products   of  more   or  less  toxic  nature. 


446  .  Disturbances  of  Digestion. 

Bile,  peptones,  ferments,  various  vegetable  acids,  gases,  the  in- 
testinal putrefaction  substances,  various  alkaloids  and  proteid 
bodies  are  to  be  met;  and  are,  it  is  true,  largely  carried  out  of  the 
system  with  the  feces,  but  to  a  certain  degree  are  also  absorbed 
by  the  portal  venous  radicles.  The  liver  serves  as  a  cleansing 
apparatus,  and  frees  the  portal  blood  from  these  harmful  ingre- 
dients. As  soon  as  the  liver  becomes  affected  by  diseases  which 
reduce  its  antitoxic  functional  ability,  these  substances  must 
necessarily  pass  through  the  organ  without  being  transformed  and 
gain  entrance  to  the  general  circulation  and  be-  changed  possibly 
by  other  tissues  or  be  eliminated  by  the  kidneys,  lungs  and  per- 
spiration. The  kidne}'-  is  particularly  capable  of  acting  in  place 
of  the  liver  in  purifying  the  blood.  It  has  been  shown  that  th^ 
urine  in  hepatic  diseases  and  in  conditions  which  cause  an  in- 
creased albumen  disintegration  (whether  in  the  liver  itself  or 
elsewhere)  acquires  decidedly  increased  toxic  properties  and 
contains  instead  of  or  along  with  urea  large  amounts  of  am- 
moniacal  compounds  or  acid  bodies,  as  amido  acids  (leucin, 
tvrosin),  aromatic  oxyacids.  acetone  and  albumoses.  Such  ma- 
terials are.  however,  injurious  to  the  kidneys  and  for  this  reason 
disease  of  the  liver  is  frequently  complicated  by  pathological 
changes  in  the  kidneys.  In  case  of  failure  of  the  compensatory 
function  of  the  kidneys,  and  especially  if  poisonous  substances  no 
longer  neutralized  by  the  liver  parenchyma  are  passing  into  the 
blood,  there  may  ensue  symptoms  of  general  intoxication  acting 
particularly  upon  the  central  nervous  system.  These  phenomena 
may  be  met  in  varying  grades  of  severity,  as  convulsive  or  stupor- 
ous conditions  of  acute  or  protracted  course,  according  to  the 
extent  of  destruction  of  liver  cells,  the  increase  of  albuminous 
■disintegration  in  the  liver  and  the  access  of  infectious  factors. 
The  most  important  poisonous  material  wdiicli  occurs  in  case  of 
destruction  of  the  hepatic  function  concerned  in  the  transforma- 
tion of  albuminates  into  urea  and  uric  acid,  is  carbamic  acid  :  the 
entrance  of  this  material  into  the  blood,  as  seen  in  animals  de- 
prived of  the  liver  or  having  an  Eck's  fistula  (Minkowski*),  causes 
very  intense  cerebral  disturbances. 

Stagnation  of  bile,  besides  causing  biliary  staining  of  the  liver 
and  the  rest  of  the  body  structures,  the  so-called  icterus  (x.  p. 
212),  is  also  responsible  for  cerebral  toxic  symptoms  (spasms 
and  stupor),  because  of  complex  conditions  of  intoxication   simi- 

♦  For  details  see  Kitt,  Pathol.  Andtcnnie  iler  Haitstinc,   II   Aiifl.    1   Bd.,   p.   595. 


Diseases  of  the  Pancreas.  447 

lar  to  the  above.  The  choHc  acid  especially  is  toxic  to  the  nerv- 
ous structures,  but  the  biliary  pigments  are  not  entirely  inert;  and 
haemolysis  also  plays  a  part  {chohonia).  Obstruction  of  bile 
from  the  intestine  and,  too,  diminished  or  completely  checked 
production  of  bile  -{oligocholia,  acholia),  because  of  degeneration 
of  the  hepatic  parenchyma,  disturb  the  formation  of  the  chyme; 
absorbtion  of  fat  is  made  difficult  in  the  absence  of  bile  and  the 
loss  of  the  antiseptic  influence  of  bile  may  cause  intestinal  catarrh 
from  putrefaction  of  the  ingesta. 

Hepatic  diseases  also  affect  the  nutrition  of  the  tissues,  from 
bringing  about  changes  in  the  character  of  the  blood.  The  Hver 
is  the  storehouse  for  the  sugar  of  the  blood  (E.  Voit),  which  it 
elaborates  from  the  material  brought  to  it  from  the  intestine  by 
the  portal  vein ;  it  stores  up  fat,  and  consumes  the  debris  of  broken 
down  corpuscles;  and  in  case  of  loss  of  these  functions  the  body 
must  suft'er  from  the  abnormalities  in  some  of  its  important 
sources  of  energy.  Further  there  may  be  mentioned  altera- 
tions which  are  brought  about  by  mechanical  interference  with 
the  blood  circulation,  as  in  diffuse  induration  of  the  liver;  all  dis- 
eases which  tend  to  occlude  the  blood  capillaries  and  cause  com- 
pression and  narrowing  of  the  innumerable  intrahepatic  ramifica- 
tions of  the  portal  vein  bring  about  passive  congestion  of  the 
organs  in  which  the  portal  vein  originates,  the  stomach,  intestine, 
spleen,  and  the  visceral  portion  of  the  peritoneum.  From  this' 
condition,  dropsical  transudation,  ascites,  is  apt  to  develop. 

Diseases  of  the  Pancreas. — Diseases  of  this  organ  causing 
atrophic  changes  of  the  glandular  parenchyma,  render  the 
formation  and  discharge  (into  the  intestine)  of  its  secretion 
impossible,  have  an  important  influence  upon  digestion  of  proteids 
and  absorbtion  of  fats,  may  be  followed  by  diabetes,  and  lead  to 
serious  and  progressive  emaciation.  Especially  in  case  of  the 
horse,  an  animal  possessing  a  relatively  small  stomach  and  only 
a  short  period  of  gastric  digestion,  the  loss  of  the  pancreatic  func- 
tion cannot  be  compensated  for  by  other  glands  and  gives  origin 
to  a  fatal  cachexia  (Siedamgrotzky).  Observations  on  dogs,  cats, 
hogs,  rabbits,  pigeons,  birds  of  prey,  after  extirpation  of  the  gland 
or  restriction  of  its  secretion  from  the  intestine  by  ligature  of 
the  duct,  have  shown  that  in  case  of  failure  of  the  pancreatic 
jivce  fats  are  no  longer  absorbed  (only  in  natural  emulsion  is 
fat  absorbed  to  the  extent  of  thirty  to  forty  per  cent. ;  all  the 
neutral   fat  reappears  in   the   feces;  and  only  part  of  the  fats   is 


448  Disturbances  of  Rcspiratioii. 

split)  ;  only  about  forty-four  per  cent,  of  the  proteids  are  absorbed 
(Abelmann,  Krelil),  and  sixty  to  eighty  per  cent,  of  the  carbo- 
hydrates. The  latter  and  the  sugar  formed  within  the  body  from 
the  albumens  are  excreted  unchanged  in  the  urine  (Minkowski). 
The  diabetes  thus  produced  varies  in  its  severity  according  as  to 
whether  the  gland  has  been  completely  or  only  partially  removed 
in  operation,  whether  it  is  generally  involved  by  disease,  or 
whether  portions  of  the  gland  remain  in  functionating  condition. 
In  dogs  and  cats  after  total  ablation  of  the  organ,  the  urine 
usually  contains  as  high  as  eight  to  ten  per  cent,  of  sugar ;  and 
the  animal  may  be  expected  to  die  from  the  progressive  cachexia 
in  the  course  of  fifteen  to  twenty  days.  Diabetes  fails,  if.  in  ex- 
perimental removal,  a  sufiicient  amount  of  the  gland  is  left  or 
transplanted  under  the  skin  ;  and  occlusion  of  the  duct  (ligature, 
obstruction  by  calculi)  does  not  invarial)ly  cause  diabetes,  as 
the  secretory  substance  may  then  be  absorbed  through  the  lym- 
phatics and  be  conveyed  to  the  blood.  The  active  agent  involved 
is  believed  to  be  a  ferment  whose  function  is  the  destruction  of 
the  sugar  in  the  blood ;  if  this  be  wanting  the  sugar  necessarily 
accumulates  in  the  blood  and  passes  unchanged  into  the  urine. 
It  is  of  further  interest  to  recall  that  in  diffuse  carcinomatosis  of 
the  pancreas  diabetes  may  similarly  be  absent,  apparently  because 
the  tumor  cells,  as  the  offspring  of  the  secreting  gland  cells,  are 
capable  of  carrying  on  the  function  of  the  latter  to  an  extent  suffi- 
cient for  the  metaboHc  demands  in  this  direction. 

The  effects  of  failure  of  the  pancreatic  juice  to  pass  into  the 
intestine  mav,  in  normal  conditions  of  the  intestine,  be  practically 
compensated  (not  in  tlie  horse — v.  supra)  by  tlie  fat-splitting 
power  of  the  bile  and  the  intestinal  bacteria,  the  latter  causing 
proteid  putrefaction  at  the  same  time. 

Disturbances   of   Respiration. 

The  constant  intake  of  oxygen  and  output  of  carbonic  acid 
gas  is  the  first  vital  requirement  of  the  cells  of  the  animal 
body.  In  foetal  life  this  interchange  of  gases  is  performed  by 
means  of  the  placental  circulation,  in  post-natal  life  by  the  en- 
trance of  atmospheric  air  to  the  respiratory  surfaces  of  the  lungs; 
and  the  red  blood  corpuscles  act  as  essential  agents  in  causing 
the  interchange.  The  inspiration  of  the  atmospheric  air  and  flie 
output  of  that  which  has  been  rendered  unfit,  constituting  what 
is  known  as  the  external  respiration,  may  be  impaired  by  closure 


Faults  of  External  Respiration.  449 

and  constriction  of  the  respiratory  passages,  diminution  of  the 
respiratory  surfaces  of  the  Kings,  and  by  any  interference  with 
the  movements  of  the  respiratory  muscles.  In  conditions  of  ob- 
struction of  the  nasal  passages  (swelHng  of  the  nasal  mucous 
membrane,  tumors),  breathing  may  for  the  time  be  still  accom- 
plished through  the  mouth;  obstruction  of  the  larnyx  and  tra- 
.chea  with  its  branches,  by  foreign  bodies  or  tumors  in  the  lumen, 
spasm  of  the  glottis,  external  pressure  (thyroid  tumors,  oesopha- 
geal diverticula,  strangulation),  or  collection  of  exudates  in  the 
tubes,  causes  difficulty  of  respiration  (dyspna^a,  air  hunger)  in 
proportion  to  the  extent  of  the  obstruction.  Proportionately  to 
the  degree  of  diminution  of  entrance  of  air  to  the  lungs  the  blood 
becomes  impoverished  in  oxygen  and  its  carbonic  acid  content 
increases.  Lack  of  oxygen  and  excess  of  carbonic  acid  in  the 
blood  act  to  stimulate  the  respiratory  centre  in  the  medulla  ob- 
longata (point  of  exit  of  the  vagus)  ;  this  stimulation,  and  prob- 
ably the  mechanical  influence  of  incomplete  filling  of  the  pulmo- 
nary alveoli,  which  directly  afifects  the  fibres  of  the  vagus,  bring 
about  an  increased  contraction  of  the  inspiratory  muscles.  In- 
spiration becomes  stronger,  more  powerful,  deeper  and  longer 
in  duration,  because  the  narrowed  lumen  of  ihe  tubes  does  no't 
admit  the  external  air  to  pass  readily  into  the  alveoli  and  the  de- 
mand for  oxygen  in  the  medulla  oblongata  is  not  at  once  satis- 
fied (Krehl).  The  air  becomes  rarified  in  the  lung  and  the  in- 
tra-alveolar  pressure  less  than  the  external  pressure  upon  the 
outside  of  the  body;  and  for  this  reason  inspiratory  retractions  oi 
the  intercostal  tissues  may  be  noted.  Because  the  air  cannot  pass 
out  through  the  narrowed  portions  of  ^e  tract  with  the  usual 
ease,  the  lung  does  not  collapse  as  rapidly  as  normally  and  ex- 
piration is  also  prolonged   (Krehl). 

Contraction  of  the  diaphragm  is  the  main  factor  of  the  inspir- 
atory forces,  the  contraction  of  this  broad  muscular  sheet,  arch- 
ing anteriorly  .  because  of  the  pressure  oi  the  abdominal  viscera, 
causes  it  to  assume  a  flatter  plane  and  thus  increases  the  thoracic 
space,  the  elevation  of  the  chest  wall,  especially  the  lower  ribs 
(by  the  levator  costarnm  muscles)  aiding  in  producing  this  ef- 
fect. Expiration  is  due  to  cessation  of  the  diaphragmatic  contrac- 
tion (termination  of  its  tension)  and  that  of  the  levator  muscles,  as 
well  as  to  the  elastic  contraction  of  the  lung  expanded  in  inspira- 
tion. Ruptures  of  the  diaphragm  (excluding  here  the  question 
of   hcxmorrhage    from   the   ruptured   blood   vessels    and   hernia   of 


450  Disturbances  of  Respiration. 

the  abdominal  viscera  into  the  thoracic  cavity)  usually  rapidly 
cause  death  because  of  the  resulting  impossibility  of  breathing. 
Difficulty  of  respiration  is  similarly  occasioned  by  embarrassment 
of  and  pressure  upon  the  diaphragm  by  meteorism  of  the  abdom- 
inal organs,  tumors,  etc.,  where  the  alteration  of  contracting 
movements  and  resting  stages  is  lost  in  consequence  of  tetanic 
spasm  of  the  thoracic  muscles  and  diaphragm.  When  air  gains 
entrance  to  one  of  the  pleural  spaces  because  of  a  wound  of  the 
thoracic  wall  or  rupture  of  the  lung  (perforating  wounds,  rupture 
of  suppurating  foci),  the  lung  afifected  contracts  from  the  action 
of  its  elastic  tissue  and,  because  being  no  longer  impervious  to 
air,  it  must  adapt  itself  to  the  intrathoracic  conditions  (the  me- 
diastinum is  pressed  toward  the  opposite  side  by  the  entering  air 
and  may  even  be  ruptured) ;  expansion  of  the  lung  is,  therefore, 
no  longer  possible,  as  the  organ  cannot  follow  the  movements  of 
the  chest  wall  and  lies  loosely  (that  is.  fixed  only  at  its  root)  in 
the  chest  cavity.  The  thorax  and  lungs  cannot  properly  expand 
and  collapse  if  the  chest  cavities  are  occupied  by  fluid  exudates 
(dropsy,  pleurisy),  or  if  the  respiratory  surfaces  of  the  lungs  are 
lessened,  if  a  greater  or  less  portion  of  the  pulmonary  alveoli  are 
filled  up  or  solidified  by  pressure  of  collections  of  exuded  material, 
tumors  or  parasites  and  thus  deprived  of  their  air.  However, 
even  on  the  contrary  if  the  lungs  are  excessively  inflated,  over- 
distended,  a  condition  known  as  emphysema,  aeration  of  the  or- 
gans and  interchange  of  gases  with  the  blood  are  impaired ;  the 
lung  not  collapsing  properly  in  this  condition,  the  air  escaping 
with  difficulty  ( the  carbonic  acid  is  unable  to  pass  out  by  dif- 
fusion to  a  sufficient  degree),  f.nd  the  capillaries  narrowed  by 
being  stretched  and  not  permitting  the  blood  to  flow  readily  through 
their  lumina.  Under  any  such  condition  breathing  becomes 
labored  and  air  hunger  becomes  apparent.  In  addition  circula- 
torv  disturbances  are  induced,  sometimes  due  to  pressure  upon 
the  thin  walled  veins  bv  accumulations  of  fluid  in  the  chest  cavity 
and  bv  the  uninterrupted  enlargement  of  volume  of  the  lungs, 
this  causing  congestion  in  practically  all  of  the  veins  (v.  dropsy), 
the  factor  of  aspiration  of  venous  blood  fails ;  and  as  terminal 
features  difficulties  of  discharge  of  the  blood  from  the  right  heart 
grow  apace  (resistance  in  pulmonary  arterial  area),  if  the  vas- 
cular distribution  in  the  lungs  be  embarrassed  by  pressure  or 
obstructive  influences  ( secondary  cardiac  hypertrophy  and  dila- 
tation). 


Respiratory  Motor  Disturbances.  451 

In  some  affections  the  respiratory  movements  arc  accelerated 
and  more  or  less  superficial.  Increased  frequence  of  respiration 
is  met  particularly  in  febrile  affections  and  inflammatory  affec- 
tions involving  tlie  bronchioles.  The  causes  underlying  rapid  and  at 
the  same  time  superficial  breathing  are  not  understood;  it  is  sup- 
posed that  the  responsible  influences  are  related  with  the  in- 
creased internal  temperature  or  some  irritation  of  the  sensory 
vagus  filaments.  Respiratory  disturbances  may  also  be  brought 
about  bv  cerebral  lesions.  Affections  of  the  nervous  substance 
of  the  brain  which  do  not  induce  paralysis  of  the  medulla  oblon- 
gata, accumulation  of  fluid,  parasites,  haemorrhages  or  toxic  and 
infectious  irritants,  may  cause  an  increase  of  intra-cerebral  pres- 
sure, this  apparently  disturbing  the  stimulation  of  the  respiratory 
centre,  respiration  becoming  slowed  even  though  the  air  is  not 
in  anv  way  obstructed  in  its  passage  to  the  alveoli. 

When  the  inspired  air  contains  poisonous  gases,  it  is  to  be 
expected  that  according  to  the  character  of  these  substances  and 
their  quantitative  admixture  in  the  atmosphere  there  will  be  man- 
ifested either  violent  coughing  or  suffocative  symptoms  (ammonia 
for  example)  ;  and  inflammatory  local  disturbances  will  be  induced 
(inhalation  of  formol  vapor)  ;  or  that  some  blood  change  (as  in 
carbon  monoxide  poisoning)  will  be  brought  about  by  limitation 
of  the  atmospheric  oxygen  and  alteration  of  the  haemoglobin. 

The  respiratory  variations  are  the  result  of  regulative  pro- 
cesses set  into  activity  automatically  and  reflexly  by  the  respira- 
torv  centre.  Deeper  or  accelerated  respiratory  movements  may, 
to  a  greater  or  less  degree,  compensate  for  faults  of  gaseous  in- 
terchange of  the  blood  and  the  tissues.  \Mth  cessation  of  the  fault, 
as  by  removal  of  an  obstruction  to  the  entrance  of  air  to  the  lungs, 
and  coincidently  with  the  moment  when  the  medulla  oblongata 
again  receives  a  proper  amount  of  oxygenated  blood,  the  special 
stimulation  of  the  centre  ends  and  the  respiratory  movements  again 
become  normal.  Where  the  causes,  however,  continue  operative 
and  become  more  marked,  and  even  the  excited  respiratory  move- 
ments finally  become  incapable  of  relieving  the  air  hunger  of  the 
tissues,  asphyxia  (siiffocatiou)  must  ensue.  As  long  as  the  brain 
retains  its  normal  irritability  the  labored  and  deep  respiratory 
efforts  indicate  medullary  irritation,  and  in  the  latter  case  the 
rate  of  cardiac  action  is  also  slowed  from  the  marked  irritation 
of  the  vagus,  and  the  cutaneous  vessels  are  dilated  because  of 
irritation   of  the  vasomotor  center    (Krehl);  after   a   time   tonic- 


452  Disturbances  of  Respiration. 

clonic  convulsions  occur  and  death  follows  after  a  short  period  of 
paralysis  (Krehl).  Where  the  irritability  of  the  central  nervous 
system  is  diminished  (haemorrhages  into  the  brain,  increased 
intracranial  pressure,  toxic  or  infectious  influences)  the  symptoms 
caused  by  diminution  in  oxygen  supply  are  less  violent;  the 
gradual  and  progressive  increase  of  carbon  dioxide  produces  a 
cerebral  narcosis,  the  respiratory  movements  become  gradually 
weaker  and  life  ebbs  away  with  the  advancing  paralysis  of  the 
central  nervous  organs   (Krehl). 

The   respiratory   tubes  are  provided   with  a  number  of  pro- 
tective   mechanisms,    which    serve    to    remove    foreign    particles 
which   have  gotten   into  the  air  passages.     The. passage  to   the 
trachea   and   lungs   leads   over   an   area,    the   naso-pharynx,    richly 
inhabited  by  bacteria  and  often  the  point  of  lodgment  of  foreign 
bodies;  the  narrow  laryngeal  opening  is  the  threshold  separating 
this   septic  territory  from   the  tracheal   system.     Of   course,   the 
larger   foreign   particles   which   get   into   the   nose   and  pharynx 
and  which  irritate  the  nerves  of  the  mucous  surface  and  thus  in- 
duce  sneezing  and   snorting,   are   from   time  to  time  discharged, 
and  the   entrances  for  air  are  kept  free  for  the  passage  of  air; 
but  motile  virulent  organisms  may  easily  pass  in,  and  aspiration 
of  small  drops  of  septic  mucus  and  saliva  or  even  food  particles 
may  readily  occur.     In  this  case   (these  substances  having  passed 
into  the  trachea  and  bronchi)  the  continued  activity  of  the  ciUated 
cells  serves  to  remove  these  foreign  particles,  carrying  them  back 
to  the  trachea  and  larynx.     The  mucus   secreted  over  the  whole 
surface  of  the  tubes  serves  to  envelop  the  foreign  elements,  and, 
too,    dilutes    the    poisonous    substances   and    renders    them   inert. 
Moreover,  the  numerous  depots  of  lymphoid  cells  may  make  an 
efficient  phagocytosis  possible  and  thus  facilitate  the  removal  of 
very  minute  foreign  particles.     In  addition  the  reflex  production 
of  coughing,  which   forcibly  discharges   foreign  objects,  the   col- 
lections  of   mucus    to  which   they    are    adherent    and    any   other 
injurious  contents  of  the  trachea,  is  manifested  and  acts  to  cleanse 
the   upper   portion   of   the   tubes.     Excitation   of   cough   is   prin- 
cipally induced  by  local  irritation  of  the  sensor}^  vagus  fibres  in 
the  larynx  and  trachea,  and  may  also  originate  in  the  pleura,  a 
special  group  of  movements  of  the  respiratory  muscles  being  ex- 
cited reflexly  through  the  medulla  oblongata.     Cough  begins  with 
a  deep  inspiration,  followed  by  a  forcible  expiration ;  the  air  under 
high  pressure  in  the  lungs  forces  its  way  out  through  the  opening 


Coughing.  453 

of  the  opposing  rima  glottidis  and  drives  everything  in  the  larynx 
and  trachea  (to  a  certain  extent,  too,  that  which  is  in  the  pharynx) 
out  into  the  mouth  (Krehl).  Foreign  bodies,  exudates,  etc., 
lodged  below  the  bifurcation  of  the  wind  pipe  may  also  at  times 
be  carried  out ;  but  there  is  a  chance  that  objects  in  this  position 
may  be  driven  deeper  into  the  bronchial  tubes  (Krehl).  Expec- 
toration, removal  of  such  substances  from  the  chest  (or  better, 
the  lungs)  is  accomplished  primarily  by  the  ciliated  epithelium 
and  the  upward  convection,  by  this  means,  of  the  mucous  vehicle; 
the  stimulus  to  cough  acting  upon  the  expectorate  (sputum) 
only  from  the  level  of  the  bifurcation  upwards. 

These  defensive  mechanisms  may  be  of  no  efficience  it  the 
harmful  chemical,  bacterial  or  mechanical  agents  are  of  such  a 
character  that  they  paralyze  and  destroy  the  epithelial  cells  and 
their  ciliary  action,  and  the  phagocytes  or  the  smooth  muscles 
of  the  bronchial  tubes,  or  if  the  foreign  bodies  are  held  firmly 
because  of  swelling  of  the  bronchial  mucous  membrane,  or  if  the 
obstruction  be  tightly  fixed  because  of  its  size;  and  may  be  in- 
effective because  of  lesion  or  disease  of  the  motor  or  sensory  ap- 
paratus involved  in  coughing  movements.  The  retention  of  for- 
eign bodies  and  pathological  secretions  may  be  followed  by 
asphyxia,  because  of  the  obstruction  to  the  air  passages ;  or  may 
be  the  cause  of  such  serious  effects  as  gangrene  of  the  lung,  etc., 
as  the  obstructing  substances  usually  carry  bacteria  with  them, 
(Under  normal  conditions  the  pulmonary  alveoli,  the  bronchial 
tubes  and  trachea  are  sterile,  because  in  the  first  place  the  bacteria 
entering  with  the  air  lodge  on  the  mucous  membrane  of  the 
nose  and  pharynx,  where  the  current  of  air  first  strikes  at  an  angle 
and  sweeps  over  the  moist  surface,  and  in  the  second  place  be- 
cause they  are  carried  up  and  out  by  the  activity  of  the  ciliated 
cells.) 

The  act  of  coughing  may  itself  be  dangerous.  In  conditions 
which  increase  the  irritability  of  the  respirator}-  mucous  mem- 
brane or  of  the  pleura  T inflammations)  frequent  coughing  is  ex- 
cited without  there  being  anything  requiring  removal  in  the  air 
passages.  The  violent  expiratory  force  of  coughing  raises  the 
intra-pulmonary  air  pressure  and  may  thus  cause  pulmonary  dis- 
tension (emphysema)  :  it  interferes  with  the  return  flow  of  venous 
blood  into  the  thorax  and  heart,  to  the  extent  that  the  latter 
may  be  practically  empty,  raises  the  arterial  pressure  all  over 
the  body,  and  may  cause  rupture  of  the  vessels    (KrehlV     The 


454  Urinary  Disturbances. 

violent  respiratory  paroxysms  by  increasing  the  abdominal  pres- 
sure may  force  the  abdominal  viscera  into  abnormally  or  normally 
existing  openings  and  thus  cause  displacements   [hernia]. 

Disturbances  of  the  TJrinary  Excretion. 

The  excretion  from  the  blood  of  material  no  longer  useful  to 
the  system  through  the  kidneys,  is  subject  to  pathological  faults 
if  the  quantity  and  quality  of  the  blood  passing  through  these 
organs  are  seriously  changed,  and  if  the  renal  parenchyma  is  the 
seat  of  pathological  lesions.  Increase  in  the  quantity  of  the  urine 
(polyuria),  especially  of  the  proportion  of  water  in  it,  is  met 
when  the  quantity  of  blood  passing  through  the  kidneys  is  greater 
than  usual,  that  is.  where  arterial  pressure  is  increased  without 
any  narrowing  of  the  renal  vessels,  or  where  with  the  ordinary  , 
blood  pressure  the  renal  vessels  are  dilated.  A  more  or  less 
marked  polyuria  is  met  in  a  number  of  the  acute  and  most  of  the 
chronic  inflammations  of  the  kidneys,  and,  too,  after  administra- 
tion of  diuretic  drugs,  in  connection  with  certain  intoxications 
(mouldy  oats,  cantharidts,  colchicum,  oil  of  turpentine),  after 
resorption  of  transudates  and  exudates,  in  the  stage  of  crisis  in 
febrile  infectious  disease  and  in  the  conditions  spoken  of  as  dia- 
betes insipidus  and  diabetes  mellitus.  It  may  be  readily  under- 
stood that  to  a  certain  degree  this  phenomenon  is  due  to  chemical 
stimulation  of  the  renal  parenchyma  with  secondarily  increased 
permeability  of  the  dilated  blood  vessels,  or  to  increased  secretory 
action  of  the  vascular  endothlium  and  renal  epithelium:  on  the 
other  hand  the  causes  of  the  increase  of  blood  pressure,  apart 
from  increased  ingestion  of  fluids,  are  as  yet  by  no  means  clear. 
Cardiac  hypertrophy,  vaso-motor  disturbances  originating  in  the 
medulla,  and  paralysis  of  the  renal  nerves  are  worthy  of  consid- 
eration in  this  relation.  The  causative  factors  underlying  the 
large  output  of  urine  occurring  in  so-called  urinary  flux  or  diabetes 
isipidus  ( Siapaivu.  to  pass  through;  insipidus,  tasteless — in  dis- 
tinction from  diabetes  mellitus)   are  equally  obscure. 

Better  information  obtains  in  regard  to  the  causes  of  diminu- 
tion of  the  quantity  of  urine  (oliguria)  and  of  total  suppression 
of  urine  (anuria).  It  must  be  obvious  that  all  conditions  in 
which  the  urinary  passages  are  obstructed,  as  the  urethra  and 
ureters,  by  calculi,  tumors,  strictures,  occlusion  of  the  collecting 
tubules  of  the  renal  papill?e  by  the  shrinkage  of  the  connective 
tissue    about    them    or   the    retention    of   urinary    casts,    plugs    of 


Albiiiiiiiiitria.  455 

exudate,  etc..  must  offer  a  resistauce  to  the  outflow  of  urine;  and 
any  severe  renal  inflammations  in  which  the  epithehal  cells  be- 
come degenerated  must  reduce  or  stop  entirely  the  secretory 
power  of  the  organ.  In  the  first  group  the  urine  is  danmied 
back  and  pressure  atrophy  of  the  renal  parenchyma  takes  place, 
the  cortical  portion  continuing  to  secrete  for  a  time  and  urine 
being  unable  to  escape ;  and  in  the  other  type  of  cases  the  pas- 
sages are  open,  but  the  original  secretory  disturbance  determines 
a  diminished  production  and  a  pathological  composition  of  the 
urine.  In  case  of  unilateral  disease  such  faults  may  be  compen- 
sated by  the  opposite  organ  which  remains  functionally  capable, 
which  receives  a  larger  proportion  of  the  substance  requiring  ex- 
cretion in  the  urine,  functionates  more  freely  and  becomes  hyper- 
trophied.  The  secretion  of  urine  nni«t  decrease  also  in  conditions 
in  which  a  diminished  amount  of  blood  flows  into  the  kidneys  as 
the  result  of  narrowing  of  their  blood  vessels,  as  from  shrinkage 
of  the  renal  capillaries  and  atrophy  of  the  glomeruli  ( in  chronic 
interstitial  nephritis),  from  thrombosis  of  the  renal  arteries,  or 
notably  from  lowering  of  blood  pressure  as  in  cardiac  failure  and 
a  number  of  the  above  mentioned  conditions.  In  the  same  way 
a  reduction  in  the  output  of  urine  takes  place  when  large  quan- 
tities of  fluid  escape  from  the  body  by  other  routes  or  where  the 
fluid  is  kept  back  in  the  tissues  as  in  fevers,  diarrhceas,  or  forma- 
tion of  fluid  exudates  and  transudates  in  the  body  cavities. 

One  of  the  most  important  pathological  phenomena  is  the  ex- 
cretion of  albumen  with  the  urine,  alhniuiunria.  In  normal  con- 
ditions, at  least  in  states  in  which  it  is  impossible  to  clearly  dis- 
tinguish between  normal  and  pathological  conditions,  it  is  true 
there  is  a  very  small  quantity  of  the  blood  albumen  passed 
through  the  kidneys,  so  small  tb.at  it  can  only  be  recognized  in 
nurposefully  concentrated  urine  and  by  special  methods  of  de- 
termination, as  after  fatigue  from  physical  exertion  (so-called 
physiological  and  accidental  albuminurias).  When  the  amount 
'^f  albumen  passed  in  the  urine  becomes  sufllicient  to  be  recog- 
nized by  the  ordinary  albumen  reagents,  there  is  reason  to  ap- 
prehend the  pathological  disturbance  of  the  renal  function.  This 
may  be  of  a  quickly  transitory  nature,  of  no  particular  importance 
and  indistinguishable  from  the  above  mentioned  non-pathogenic 
symptomatic  conditions;  but  as  a  rule  it  is  an  indication  of  some 
lesion  of  the  renal  parenchyma. 

AH    sorts    of    poisonous    substances,    both    those    of    external 


456  Urinary  Disturbances. 

source  (metallic  salts,  ethereal  oils,  etc.),  and  especially  the  tox- 
ines  of  infectious  diseases  and  the  products  of  intracorporeal 
tissue  disintegration  and  metabolism,  may  give  rise  to  lesions  of 
the  renal  epithelial  cells  and  their  basement  membranes,  making 
it  possible  for  the  albumen  of  the  blood  to  pass  through  them. 
In  most  cases  an  inflammation  of  the  organ  is  also  present,  this 
factor  introducing  additional  features  of  increased  permeability 
of  the  blood  vessels,  exudation,  desquamation  of  the  epithelium 
and  the  formation  of  albuminous  casts,  blood  casts,  etc.  Some 
authors  look  upon  evers^  albuminuria  as  the  result  of  an  exuda- 
tive nephritis  of  some  degree  of  severity,  now  unimportant,  now 
serious. 

(For  fuller  details  v.  Friedberger-Frohner,  Lehrbnch  d.  klin.  Unter- 
suchungsmcthodcn.     Verlag   von   F.    Enke,    Stuttgart,    III.    Aufl.) 

Another  important  symptom,  often  met  in  man.  but  uncom- 
mon in  animals,  is  the  excretion  of  sugar  in  the  urine.  Although 
the  blood  contains  a  considerable  amount  of  sugar  (as  much  as 
0.2  per  cent."),  only  minute  traces  pass  into  the  urine  normally. 
In  conditions  in  which  unusual  amounts  of  sugar  are  brought 
into  the  blood  {alimentary  hyperglyccemia) ,  and  the  liver  and 
muscles  are  no  longer  able  to  use  it  up,  the  kidneys  excrete  the 
excess  (glycosuria)  ;  milk  sugar  passes  most  readily  and  in  order 
thereafter  levulose.  cane  sugar  and  grape  sugar  (Krehl).  It  was 
discovered  by  Mering  that  the  administration  of  the  glucoside 
phloridzin.  which  contains  about  forty  per  cent,  of  sugar,  is  fol- 
lowed by  a  glycosuria  in  which  not  onh'  does  a  considerable 
amount  of  the  unchanged  glucoside  pass  ofif  in  the  urine,  but  also 
sugar  from  the  blood  (dextrose)  and  from  the  liver  (glycogen), 
probably  because  of  some  secondary  toxic  lesion  of  the  renal 
epithelial  cells. 

A  transitory  glycosuria,  ending  in  the  course  of  few  hours, 
occurs  after  puncture  of  Claude  Bernard's  glycosuric  point,  a 
procedure  consisting  in  making  a  fine  puncture  in  a  certain  spot 
in  the  floor  of  the  fourth  ventricle  of  the  brain.  A  similar  glyco- 
suria may  also  be  observed  after  lesions  in  other  parts  of  the 
central-  nervous  system  and  in  a  number  of  intoxications  and  in- 
fectious diseases  (as  in  morphine  poisoning,  curare  poisoning  and 
rabies).  If  the  splanchnic  be  cut  at  the  same  time,  or  the  liver 
be  extirpated,  or  if  fasting  animals  are  employed,  the  glycosuric 
puncture    does    not    succeed    or    is    uncertain,    and    therefore    the 


Diabetes  Mellitus.  457 

quantity  of  glycogen  in  the  liver  has  something  to  do  with  the 
glycosuria;  the  precise  character  of  the  nervous  influence  is,  how- 
ever, unknown. 

Where  the  excretion  is  a  persistent  and,  too,  a  progressive 
symptom,  provided  no  unusual  quantities  of  sugar  are  ingested 
with  the  food,  there  may  be  said  to  exist  a  special  disturbance  of 
metabolism,  diabetes  mellitus  (mel,  honey;  SiajSalvw, ,  to  pass 
through).  In  this  affection  even  the  ingestion  of  starch  causes 
the  appearance  of  grape  sugar  in  the  urine,  so  markedly,  in  fact. 
that  the  greatest  portion  of  the  starch  instead  of  being  assim- 
ilated passes  ofif  as  sugar;  and  the  urine  only  remains  free  from 
sugar  if  carbohvdrates  are  entirely  excluded  from  the  food  (Krehl 
and  others).  While  in  the  milder  cases  of  this  disease  the  amount 
of  proteid  ingested  has  no  influence  upon  the  glycosuria,  although 
the  sugar  is  formed  normally  from  proteid  also,  and  while  in 
these  cases  an  increased  supply  of  albuminous  diet  seems  to  be 
quite  advantageous  to  the  nutrition  of  the  body,  there  are  cases 
of  a  severe  type  in  which  even  a  strict  meat  diet  and  even  absti- 
nence from  all  food  do  not  permit  the  urine  to  become  free  from 
susrar.  Of  what  nature  the  metabolic  disturbances  mav  be  which 
ar^  responsible  for  the  imjierfect  manner  in  whicli  the  carbo- 
hydrates and  the  glycogen  formed  from  proteid  are  dealt  with  is 
still  rather  obscure  and  confused  fcf.  Krehl).  In  a  measure  the 
liver  normally  prevents  the  direct  passage  of  carbohydrates  into 
the  circulation  and  has  the  power  of  removing  sugar  from  tlie 
portal  blood  and  of  storing  glycogen.  Diseases  of  the  liver  affect- 
ing this  function  permit  a  hyperglycremia  to  develop ;  (according 
to  Bimes  it  ought  to  be  possible  to  recognize  the  existence  of 
hepatic  disease  bv  feeding  molasses,  as  in  case  the  liver  Avere 
normal  the  urine  would  remain  free  from  sugar  while  otherwise 
glucose  would  become  demonstrable  in  it).  Especial  informa- 
tion has  been  obtained  from  the  excellent  investigations  of  Mering 
and  Minkowski  in  relation  to  the  pancreas,  which  have  shown 
that  diabetes  mellitus  occurs  when  this  gland  is  lost  (extirpation 
degeneration")  and  that  either  the  pancreatic  juice  or  the  glandu- 
lar parenchyma,  the  blood  from  which  passes  to  the  liver  by  the 
portal  vein,  has  in  common  with  the  liver  a  regulative  influence 
upon  the  amotmt  of  sugar  in  the  blood  or  some  power  of  fixation 
of  excesses  of  sugar  (v.  p.  448).  [The  generally  favored  view 
at  present  among  the  profession  would  refer  the  pancreatic  fault 
to  some  disease  of  the  islands  of  Langerhans  .(Opie).     It  is  be- 


458  Urinary  Disturbances. 

lieved  that  these  special  structures  secrete  and  give  into  the  blood 
of  the  pancreatic  vein  a  substance  which  is  either  itself  a  glycolytic 
ferment  or  which  is  not  a  ferment,  but  a  more  simple  substance 
acting  to  energise  a  glycolytic  ferment  in  the  muscles  and  other 
tissues  of  the  body.  This  glycolytic  ferment  is  regarded  as  es- 
sential to  the  final  transformations  and  chemical  decomposition 
of  the  sugar  in  the  system  in  order  that  it  may  be  assimilated: 
in  its  absence  assimilation  '  is  impossible  and  the  body  suffer.^ 
by  its  inability  to  make  use  of  the  carbohydrates  furnished  to  it, 
and  at  the  same  time  the  sugar  in  the  blood  accunmlates  and 
when  in  excess   (above  0.4  per  cent.)   is  excreted  in  the  urine.] 

In  its  chronic  form  diabetes,  an  expression  of  metabolic  fault 
and  at  times  accompanied  by  fauhs  of  the  liver  and  pancreas, 
causes  more  or  less  harm  to  the  whole  body.  When  the  incom- 
plete assimilation  of  carbohydrates  is  not  compensated  by  the 
supply  of  albuminates  and  fat,  especially  when  the  associated 
diseases  do  not  permit  the  assimilation  of  these  last  named  sub- 
stances,  the  general  nutrition  must  of  necessity  fail.  In  serious 
cases  there  is  apt  to  be  present,  as  well,  a  marked  proteid  disin- 
tegration, and  albuminuria  appears  as  a  symptom,  together  with 
degeneration  of  the  lens  and  retina,  disease  of  the  blood  vessel 
walls  and  a  weakened  resistive  state  of  the  tissues,  which  induces 
s.  special  predisposition  to  tuberculosis  and  gangrene    (in  man). 

Disturbances  of  micturition  include  difficult  micturition 
(dysiiria)  caused  by  strictures  and  obstructions  to  the  pnth  of 
outflow  (the  dribbling  forced  passage,  with  tenesmus  and  frequent 
call  to  urinate,  is  called  strangury)  ;  complete  repression  of  mictu- 
rition ( ischuria,  retention  of  urine),  in  which  case  the  bladder  is 
full  because  of  spasm  of  the  sphincter  or  paralysis  of  the  detrusor 
musculature;  and  inability  to  retain  the  urine  (enuresis,  incon- 
tinentia urincr).  due  to  a  paralysis  of  the  sphincter  of  the  bladder 
developing  in  disease  of  the  spinal  cord  and  of  the  bladder  itself. 

(For    details    cf.    Friedberger-Frohner,    Klinische    Untersuchungsmetho- 
dcn.) 

Diseases  of  the  urinary  apparatus  are  more  or  less  painful ; 
affections  of  the  passages  being  particularly  apt  to  cause  intense 
pains,  to  be  attributed  in  part  to  muscle  spasms,  partly  to  me- 
chanical irritation  (foreign  bodies)  of  the  sensory  filaments  of 
the  mucous  membrane  or  to  specially  induced  irritability  (ulcers, 
abrasions,  inflammations)    of  these  filaments. 


Urccmia;  Thyroid  Disturbances.  459 

The  effect  of  disturbances  of  the  uropoietic  system  upon  the 
general  body  depends  upon  the  extent  and  the  kind  of  the 
changes.  All  the  bacterial  processes  in  the  kidneys  and  in  the 
collecting-  receptacles  (bladder,  renal  pelves)  as  well  as  the 
damming  back  of  the  urine  in  the  ureters  bilaterally,  sooner  or 
later  bring  about  symptoms  of  intoxication,  manifesting  them- 
selves especially  by  symptoms  of  cerebral  depression,  less  fre- 
quently cerebral  excitation,  included  collectively  under  the 
term  urcniiia.  This  is  partly  referable  to  the  impaired  excretion 
from  the  blood  of  substances  no  longer  of  use  in  the  economy 
and  having  toxic  influences  when  retained,  as  the  products  of 
proteid  decomposition  particularly;  and  the  kidney  is  itself  a  place 
in  which  special  metabolic  processes  are  carried  on,  the  products 
of  which,  as  hippuric  acid  ( Bunge  and  Schmiedeberg),  if  retained 
may  apparently  take  part  in  the  production  of  uraemia.  The 
regulation  of  the  proportion  of  water  in  the  blood  is  apt  to  be 
disturbed  in  chronic  renal  aft'ections  ;  and,  too,  because  of  shrink- 
age of  the  comparatively  large  capillary  area  of  the  kidneys,  a 
certain  amount  of  resistance  is  likely  to  develop  to  the  arterial 
blood  flow  ;  in  these  chronic  affections,  therefore,  hydremia,  cardiac 
hypertrophy  and  general  dropsy  may  be  expected  as  secondary 
features. 

Disturbances  of  the  Thyroid  Function- 
Destruction  of  the  thyroid  tissue  by  atrophy,  degenerative 
processes  or  heterologous  tumors,  involves  the  loss  of  an  organic 
function  of  vital  importance ;  disturbances  of  nutrition,  loss  of 
physical  strength  and  spasmodic  attacks  being  induced,  indicative 
of  a  general  autointoxication  of  the  body  and  leading  to  a  fatal 
termination.  In  case  of  total  extirpation  of  the  thyroid  gland 
[including  the  parathyroids]  intense  nervous  symptoms  (delirium, 
tetanic  convulsions,  and  so-called  tetany)  quickly  appear,  as  ob- 
served in  man.  Dogs  usually  die  after  such  operations  in  from 
three  to  twenty-eight  days  and,  too,  under  circumstances  where 
injurv  to  nerves,  etc..  cannot  be  held  responsible.  After  removal 
of  large  portions  of  the  thyroid  there  is  also  danger  of  autointoxi- 
cation. Where  the  symptoms  develop  slowly,  as  is  particularly 
true  in  pathological  atrophy  of  the  glandular  tissue,  the  resultant 
condition  is  spoken  of  as  cachexia  strumipriva  or  athyrea;  and 
besides  the  nervous  symptoms  there  may  be   observed  spasmodic 


460  Athyrea;  Hyperthyrea. 

dyspnoea,  disturbances  of  growth,  dilution  of  the  blood  and 
cutaneous  changes  (falling  out  of  hair,  thickening  and  mucoid 
degeneration  of  the  subcutaneous  tissue — myxcedema  atrophicum, 
stnimosum,  operativum).  Practically  the  same  results  are  ob- 
tained from  experiments  on  monkeys,  sheep,  goats,  hogs  and  dogs 
as  are  observed  in  man  after  goitre  operations  (Hofmeister  and 
Eiselberg). 

[The  acute  results  mentioned,  tetany,  dyspnoea,  convulsions, 
palsies  and  death  in  a  few  days  after  ablation,  are  now  generally 
attributed  to  loss  of  the  parathyroid  glandules ;  removal  of  the 
thyroid  alone  is  not  essentially  fatal,  and  is  followed  by  chronic 
metabolic  disturbances  in  animals  comparable  to  myxcedema  in 
man.  The  precise  interrelation  which  probably  exists  between  the 
thyroid  and  parathyroids  is  not  understood.] 

It  has  been  assumed  (Rogowitsch)  that  the  thyroid  gland  has 
as  its  function  the  removal  or  neutralization  of  metabolic  products 
the  retention  of  which  in  the  system  would  produce  toxic  efifects, 
that  the  organ  probably,  therefore,  elaborates  a  secretory  sub- 
stance essential  to  the  regulation  of  metabolism,  which  is  appar- 
ently carried  into  the  blood  from  the  follicles  by  way  of  the  ex- 
tremely delicate  lymph  channels  (Lubarsch).  This  assumption  is 
founded  upon  the  fact  that  a  fatal  result  of  operative  removal 
may  be  avoided  by  removing  only  one  lobe  of  the  gland  and  by 
leaving  some  remnant  of  thyroid  tissue  or  by  favoring  restoration 
of  the  tissue  by  artificial  means  (transplantation  of  thyroid,  in- 
jection of  thyroid  extract),  or  if  the  parathyroids  remain  and  take 
up  a  vicarious  [  ?]  activity.  It  seems  probable  that  the  hypophysis 
is  able  in  some  degree  to  compensate  for  loss  of  the  thyroid  by 
vicarious  hypertrophy;  at  least  in  thyroidcctomized  rabbits  en- 
largements of  the  pituitary  body  have  been  observed  (Rogo- 
witsch, Stieda,  Hofmeister). 

In  connection  with  enlargements  of  the  thyroid  {struma  hyper- 
plastica  and,  too,  carciiiosa)  a  type  of  intoxication  has  been  ob- 
served, apparently  the  very  opposite  to  that  following  extirpa- 
tion of  the  organ,  the  so-called  Basedozv's  disease  {hyperthyrea, 
dysthyrea)  ;  this  condition  is  very  like  the  symptoms  of  intoxica- 
tion which  occur  both  in  healthy  human  beings  and  animals 
after  large  doses  of  thyroid  extract,  as  accelerated  and  energetic 
cardiac  action  (tachycardia),  cardiac  dilatation  and  cardiac  hyper- 
trophy, epileptiform  seizures,  prominence  of  the  eyeballs  (goggle- 


Sexual  Dislurbonces.  461 

eyes,  exophthalmiis),  and  various  results  of  these  disturbances. 
The  condition  apparently  depends,  as  pointed  out  by  Mobius, 
Greenfield,  Rehn  and  others,  upon  a  functional  disturbance  of  the 
organ  which  occasions  either  a  quantitative  or  qualitative  change 
in  the  secretion  (an  excess  of  the  secretion  or  one  in  which  there 
is  a  chemical  change) ;  but  there  are  numerous  uncertainties  in 
relation  to  these  points,  as  for  example,  the  failure  of  a  case  of 
Basedow's  disease  to  recover  after  extirpation  or  atrophy  of  the 
gland  (Lubarsch).  Jewsejenko  claims  to  have  met  this  last  dis- 
ease also  in  animals  (dog,  horse)  ;  Reynard  and  Rongieux  have 
observed  stupidity  in  dogs  and  horses  after  development  of  goitre. 

Cretinism-  and  chondrodystrophy  have  been  regarded  as  dependent  upon 
the  thyroid  function,  but  according  to  Lubarsch's  studies  there  is  appar- 
ently  no   setiological    relationship. 

Disturbances  of  the  Sexual  Function. 

Diseases  and  congenital  anomalies  of  the  sexual  glands  render 
the  individual  impotent  to  produce  viable  offspring,  in  males  pre- 
venting formation  of  semen  or  procreation  {impotence,  impo- 
tentia  generandi  ct  coeundi),  in  female  animals  interfering  with 
ovulation,  fertilization  of  the  ovum  and  maturation  of  the  embryo 
{barrenness,  sterility).  Even  general  diseases  (as  fever,  various 
painftd  affections  of  the  muscles  and  joints,  diseases  of  the  spinal 
cord)  may  indirectly  influence  the  sexual  function  (loss  of  ex- 
citabihty,  mechanical  interferences).  According  to  Zschokke 
even  if  only  one  ovary  is  diseased  there  is,  as  a  rule,  a  disturb- 
ance of  the  general  sexual  vitality.  A  number  of  affections  of 
the  sexual  glands,  as  tuberculosis  of  the  ovaries,  chronic  inflam- 
mation or  cystic  changes  of  these  organs,  or  undescended  testicle, 
are  apt  to  be  accompanied  by  special  excitability  of  the  sexual 
appetite  (constant  rutting,  buUit.g,  horsing,  nymphomania,  saty- 
riasis), sometimes  with  violence  of  temper.  In  other  cases,  how- 
ever, destruction  of  the  sexual  glands  by  disease  or  removal  b)» 
castration  is  followed  by  suppression  of  sexual  vitality,  altera- 
tions in  the  state  of  nutrition,  and  changes  in  the  bodily  struc- 
ture (change  in  the  type  of  horns  in  oxen,  loss  of  antlers  in  stag 
and  roe-deer,  shape  of  body  approximating  female  type,  fat  ac- 
ctmiulation,  gentle  disposition    in  castrated  male  animals). 

(For   details   cf.    Zschokke,  >Dic    Unfruchtbarkcit    dcs    Rindes,    Zurich, 
1900.) 


462  Disturbances  of  Cutaneous  Function. 

Local  abnormalities  of  the  uterus  may,  in  a  mechanical  way, 
determine  the  development  of  embryonal  monstrosities  or  the 
death  and  premature  expulsion  of  the  foetus  {miscarriage,  abor- 
tion). 

In  cows  and  goats,  less  frequently  in  hogs,  a  form  of  paralysis 
not  infrequently  appears  within  the  first  few  days  after  parturi- 
tion, at  the  time  of  establishment  of  lactation,  the  so-called 
paralytic  calf-fei'cr  or  paralysis  of  parturition.  The  cause  of  the 
condition,  as  Schmidt  (Kolding)  has  pointed  out,  depends  on  an 
autointoxication  related  with  the  formation  of  colostrum.  The 
colostrum  milk  is  very  rich  in  disintegrating  epithelium  of  the 
mammary  gland  and  apparently  contains  decomposition  products 
from  these  elements,  which,  if  absorbed  in  large  amounts,  are 
capable  of  giving  rise  to  toxic  efTeets.  The  condition  is  met  espe- 
cially in  animals  producing  large  amounts  of  milk,  in  case  of  un- 
usually marked  colostrum  formation.  The  excellent  results  of 
therapeutic  measures  directed  to  reduce  the  milk  secretion  and 
causing  oxidation  of  the  poisonous  products  by  introducing  oxy- 
gen into  the  udder  and  thus  rendering  them  inert,  permit  the 
acceptance  of  Schmidt's  theory  as  well  founded. 

Disturbances  of  the  Cutaneous  Function. 

The  skin,  with  its  epidermal  covering,  is  an  organ  of  defense 
to  the  body  against  the  harmful  influences  of  the  exterior.  Any 
traumatic  denudation  of  the  papillary  layer  or  deeper  wound  de- 
stroys the  protection  it  aiTords,  and  not  only  exposes  the  denuded 
surface  to  the  drying  influences  of  the  air,  but  serves  as  a  focus  of 
entrance  of  infectious  agents  as  well,  since  the  injury  opens  easy 
access  into  the  lymphatic  paths.  Long  continued  soaking  of  the 
epiderm  causes  its  maceration  (by  nasal  discharge,  urine,  etc.), 
continuous  pressure  leads  to  callosites  or  by  contusion  at  places 
which  overlie  bony  prominences  to  ruptures  of  \\essels,  haemor- 
rhages, and  in  this  way  to  disturbances  of  nutrition  which  may 
cause  necrosis  of  the  skin  (decubitus,  decubital  gangrene).  The 
loss  of  albuminates  occasioned  by  leakage  of  lymph  in  case  of 
denudation  of  the  epiderm  (running  sores  of  the  skin  and  mouth) 
may  cause  material  deterioration  of  the  state  of  nutrition  of  the 
body  (Landois). 

To  what  extent  disturbances  may  be  caused  by  suppression 
of  the  cutaneous  interchange  of  gases   (output  of  water  and  car- 


Disltirbanccs  of  Perspiration.  463 

bonic  acid  gas  in  the  perspiration)  we  have  but  Httle  knowledge. 
According  to  Ellenberger  in  horses,  which  were  shaved  and  then 
covered  with  a  coat  of  varnisli,  there  appeared  slowing  of  respira- 
tion, acceleration  of  pulse,  a  fall  of  the  body  temperature  of  one 
to  one  and  a  half  degrees  centigrade,  symptoms  of  uneasiness, 
muscular  twitchings,  polyuria  and  increa'sed  excretions  of  urea, 
these  symptoms  soon  disappearing;  the  animals  took  their  food 
without  being  at  all  urged  and  at  the  end  of  the  experiment 
showed  a  greater  body  weight  than  at  the  start.  Hogs  and  dogs, 
after  being  varnished,  showed  no  disturbances  of  health  beyond  a 
depression  of  the  body  temperature  (cited  from  Schindelka). 
Sheep,  however,  after  being  coated  with  varnish,  apparently  suffer 
considerably  (Ellenberger),  and  rabbits  die  if  no  more  than  one- 
eighth  of  their  body  surface  be  covered  with  varnish,  apparently 
because  of  excessive  heat  dissipation  (Landois,  Fourcault,  Bec- 
querel  and  Brechet) ;  in  case  the  whole  surface  of  the  body  is 
varnished  the  temperature  at  once  drops   (to  19^  C). 

For  consideration  of  chilling  of  the  skin.  cf.  p.  45. 

Because  of  the  vast  numbers  of  sensory  nerves  ending  in  the 
skin  tiie  least  denudation  of  the  papillary  layer  and  inflanmiator\- 
swelling  of  the  cutis,  as  well  as  contact  with  foreign  bodies,  oc- 
casion marked  sensations  of  pain.  .    . 

Pathological  increase  of  ])erspiration,  liypcridrosis  (i8p6w,  to 
sweat),  may  be  met  in  a  great  variety  of  conditions  which  give 
rise  to  an  excited  state  of  the  perspiratory  centres  in  the  medulla 
oblongata  and  cord  (excess  of  carbon  dioxide  in  the  blood,  de- 
ficiency of  oxygen,  sensory  and  psychic  stimulation).  Sweating 
may  be  general  or  local,  sometimes  unilateral,  or  limited  by  a  trans- 
verse border  strictly  to  the  posterior  portion  of  the  body.  In 
these  latter  examples  disturbances  in  the  nervous  distribution  are 
usually  at  the  bottom  of  the  trouble  ;  the  abnormality  is  especially 
striking  in  dogs  which  do  not  sweat  normally. 

Diminished  secretion  from  the  glands  allied  to  sweat  glands, 
which  are  met  in  the  nmzzles  of  the  ruminants,  the  snout  in  pigs 
and  nose  in  dogs,  as  a  result  of  which  these  parts,  otherwise 
always  moist,  come  to  feel  (lr\ ,  is  a  marked  symptom  in  all  febrile 
diseases. 

In  case  of  the  entrance  of  urine  into  the  peritoneal  caviiy 
after  rupture  of  the  bladder,  or  in  urinaty  infiltration  of  the  cellu- 
lar tissue  after  rupture  of  the  urethra,  the  perspiration  may  take 


464  Disturbances  of  Cutaneous  Function. 

on  a  urine-like  odor;  and  in  distemper  in  dogs  and  in  the  pock  of 
sheep  the  skin  gives  off  an  unpleasant,  offensive  odor. 

A  rough,  bristling  appearance  of  the  hair,  brittle,  dry  wool, 
is  a  symptom  of  chronic  nutritive  fauhs;  the  same  may  be  said 
of  diminution  of  the  subcutaneous  fat,  when  it  becames  tight,  in- 
elastic and  adherent  to  the  underlying  fascise  (so-called  hide- 
binding  of  the  skin). 

(For  details  v.   Friedberger-Frohner,  Lehrhuch   d.   klinisch.    Untersiich- 
ungstnethodcn   f.   Ticrarzte,  Verl.  von  Ferd.   Enke,   Stuttgart,   III.   Auil.) 


O---  THE      '^ 

UNIVERSITY 


I'latc  I. 


Fig.   1.     Acute   fibrinous   pleurisy   of   horse.     Yellow   fibrinous   exudate   spread 
over  tne  reddened,  somewhat  clouded,  pleura  of  the  right  lung. 


I 


"^..A 


lung. 


Fig.    2.     Chronic    cheesy    tuberculous    pneumonia.     Section    of    lobe    of    cow's 


^-     THE 

DIVERSITY 

OF 


rioic  II. 


Fig.   1.     Gangrene  of  skin   of   lower  jaw   of   hog. 


-s 


\ 


% 


Fig.  2.      Hyperaemia  of  sl<in   in  swine  erysipelas. 


/ 


,^ 


Fig  1.  Section  of  scrotum  of  bull  with  cheesy  coagulation  necrosis  of  tes- 
ticle: the  scrotal  sac  was  filled  with  a  sero-purulent  exudate:  the  tunica  vagmahs 
communis  and  subcutaneous  tissue  were  surrounded  by  a  dense  abscess  capsule, 
and   a   large   blood  clot   was  seen   distributed  throughout   the  sac. 


Fig.  2.      Focalized   necrosis  of   liver  of  cow:   the  section   shows  the   nodules  of 
coagulation   necrosis  of  natural   size. 


■  t  J 


ri<(lr    I 


Fig.    1.      Acute    croupous    enteritis;    a    portion    of    cow's    intestine    laid    open; 
the   mucous  membrane  is  the  seat  of  hyperaemia   and  false  membrane  formation. 


X    V 


Fig.   2.      Fatty    hvc  of    hog. 


OF  THE 


UNIVERSITY 

OF 


INDEX 


A  PAGE 

Actinomycosis    3iS 

Fungous  Growths  of  320 

"  Fungus   of    321 

Actmomycotic   Abscesses 320 

"  Nodules    320 

Active  Hyper3emia   112 

Immunization     2S 

Acute   Diseases    95 

Adenocarcinoma     39i)  407 

Adenocystoma     4^8 

Adenofibroma  Pericaniliculare   .  .  390 

Adenoma    388 

^Etiology   of 391: 

"  Varieties    of    389 

Adenosarcoma    39i 

Agglutinins    26 

Air  Embolism   149 

"     Hunger    449 

Akinesis    429 

Albuminous  Degeneration   190 

Albuminuria    455 

Alexins 19 

Algor    Mortis    104 

Alimentation,  Disturbances  of . . .     36 

Amaurosis     433 

Amblyopia   433 

Amboceptor    25 

Amputation   Neuroma    250,  358 

Amyloid  Degeneration    205 

''  "       of   Liver    .  . .   207 

"        "    Spleen    .  .  208 

"        Reaction     206 

Ansemia    1 18,  157 

Anaemic   Infarct    145 

Anassthesia    432 

Anamnesis     93 

Anasarca    130 

Anatomical-pathological     Proces- 
ses          3 

Anatomical   T\pes   of<  Inflamma- 
tion   and    Exudate 272 

Angioneurosis    435 

Angioplasts    240 

Animal  Parasites    76 

"         Poisons    51 

Ante-mortem   Clots    132 

Anthracosis     215 

Antibodies    22 


PAGE 

Antitoxine     24 

Anuria    454 

Apoplexy     425 

Apparent   Death    ■ 105 

Argyria    215 

Aristotole    11 

Ascites     130,  447 

Asphyxia    38,  45i 

"         as  Cause  of  Death....     39 

Ataxia    429 

Athyrea    459 

Atony  of  Stomach 439 

Atrophy    185 

Causes  of   186 

Autoblastomata    325 

Autochthonous  i\Ielanosis    209 

"  Thrombi   136 

B 

Bacillus   ]\Iallei    311 

Bacteria    54 

"         Mode  of   Invasion  of.  .     61 

"         Specific   Action  of 67 

Bacterisemia    66 

Basedow's  Disease  460 

Bile,  Abnormal  Secretion  of . . . .  446 

Biliary   Stasis    212,  446 

Blood    Corpuscles,    Regeneration 

of   251 

Blood,  Impoverishment  of 157 

"       Pathological  Changes  of.    156 

"      Variations   in    Ill 

.  "      Vessels,  Regeneration  of.  240 

Bone,  Regeneration  of 246 

Botryomycosis    324 

"  Fungus  of 324 

Brain,  Compression  of  425 

"  "  Svmptoms  of  425 

"       Stroke    ' 425 

BufYy  Coat    131 

Burns    42 

Fatality   of    43 

C 

Cachectic   CEdema    128 

Cachexia     190 

of  Cancer    4^4 

"         Strumipriva    459 


466 


Index. 


PAGE 

Cadaveric   Clots    132 

Calcification    216 

Calculi     216,  219 

Biliary    222, 

Intestinal    226 

"       Required   Conditions   of.   219 

"        Salivary    225 

"        Urinary    220 

Callus    247 

Cancer    394 

Cachexia   of    414 

Cellular  Morphology  of.  402 

Colloid    412 

Cylindrical   Cell    406 

"        Dissemination    of    400 

Glandular  Cell    406 

"        Gross  Appearance  of   .  .  .   410 

"       Metastasis   of    401 

Origin  of   396 

Pearls    405 

"        Scirrhus    413 

"        Transplantation  of   398 

Varieties   of    403 

Carcinoma     394 

Cardiac   Hypertrophy    106 

"  Insufficiency   109 

Cardinal    Symptoms 260 

Cartilage,   Regeneration   of 246 

Caseation     I79 

Catalepsy     428 

Catarrhal    Exudate    273 

Catching  Cold   45 

Causes  of  Disease 35 

Cavernous   Hsemangioma    ...362,363 

Cellular    Pathology    14 

Cerebro-spinal   Concussion    424 

Cheesy  Tuberculous  Infiltration.  306 

Chemical   Agents    50 

Chemico-pathological    Processes.       4 

Chemotaxis    18,  161 

Chilblain    45 

ChoLiemia     447 

Cholelithiasis     223 

Cholesteatoma    382 

Cholesterin    195 

Chondroma    35^ 

Chronic  Diseases    95 

Chronic    Inflammation    284 

Circulation,    Disturbances    of....   106 

Circulation,    Schema   of 140 

Classification      of      Inflammatory 

Processes     288 

Clinical   Observation    

Clonic    Spasms    428 

Clot,  Absorption  of   125 

"      Formation 131 

Cloudy  Swelling  190 

Coagulation    Necrosis 179 

Coagulins    26 

Cohnheim's  Theor>'   2)2)(> 


PAGE 

Colic    444 

Collateral   Circulation   143 

CEdema     128 

Colloid   Degeneration    204 

"         Substances    204 

Coma    425 

Commotio  Cerebri    424 

Comparative   Pathology    14 

Compensation      for      Circulatory 

Abnormalities     106 

Compensatory   Hypertrophy    ....   255 

Complements     I9>     25 

Complications     99 

Concretions     216,  219 

Concussion   50,  424 

Congenital   Diseases    30 

Connective   Tissue,    Regeneration 

of 237 

Consciousness,   Loss   of 424 

Consecutive  Thrombi    136 

Constipation    443 

Constitutional   Predisposition    ...     31 

(Contagious  Diseases    71 

Continued  Fever 173 

Convalescence    I73 

Convulsions    428 

Corpora  Amylacea   208 

Flava    208 

"         Versicolorata    208 

Corrosive    Poisons    52 

Cough    452 

Cramp    428 

Croupous    Exudate    275 

Inflammation   275 

Cruor    Sanguinis    131 

Cylindrical   Cell   Cancer 406 

Cylindroma     382 

Cystic   Tumors    415 

Cystoma    Penniferum    417 

Cj'tolysins    25 

D 

Death    loi 

"       Agony     103 

"       Causes  of   102 

"      Local    176 

Signs   of    104 

Decubitus    462 

Degenerative  Processes — 

Albuminous     190 

Amyloid     205 

Colloid    204 

Fatty     192 

Hyaline    I99 

Mucoid    202 

Delirium    426 

Demarcating  Inflammation  .  .  184,  2fcg 

Depression   of  the   Brain 425 

Dermoid   Cysts    416 


Index 


467 


PAGE 

Diabetes  Insipidus    454 

Mellitus    448,  457 

Diagnosis    Qi;    9i 

Diapedesis     120 

Diarrhoea  442 

Digestive    Disturbances    436 

Dilatation  of  the  Heart 109 

Diphtheritic    Inflammation    ......   276 

Direct  Symptoms   92 

Disease   i 

"        Causes    of    35 

Conception   of    2 

Course  of   91-     94 

Periods  of   96 

"        Recovery  from 100 

Symptoms    of    91,     99 

"        Termination    of    •  ■     99 

Diseases.    Congenital   and   Inher- 
ited      30 

Diseases  of  First  Stomach 439 

"    Intestines     44° 

"Jaw     436 

"    Liver 444 

"    Mouth    436 

"    CEsophagus     437 

"    Pancreas    447 

"    Pharvnx    437 

"    Stomach    437 

"    Teeth 436 

Dissemination    of    Germs    in    the 

Body     65 

Disturbances      of      Alimentation 

and     Nutrition 3^ 

Disturbances  of  Circulation 106 

Disturbances    of     Excretion       of 

Urine    •.  •  454 

Disturbances  of  Function  of  Skin  462 
Disturbances  of  JNIetabolism    ....    165 
Disturbances  of  Respiration    ....   448 
Disturbances    of     Sexual     Func- 
tion      461 

Disturbances    of    Thyroid    Func- 
tion       459 

Dizziness     424 

Dropsical   Transudate    129 

Dropsy     126 

Dwarfism    3^ 

Dyspepsia 438 

Acida    438 

Dysperistalsis 443 

DyspncEa    449 

Dysuria    458 

E 

Ecchondroma    35i 

Ecchymoses     122 

Ectogenous   and   Entogenous    In- 
fectious  Agents    70,     71 

Ehrlich's   Theory    22 

Electrical   Influences    48 


PAGE 

Emboli 131,   138,  149 

"       Course  of   I39 

Embryoma     421 

Emphysema     450)  453 

Empyema     281 

Enchondroma    35^ 

Endarteries    I44 

Endemic   Disease    72 

Endothelioma    380 

Endotoxines     58 

Enostoses    354 

Enteroliths    227 

Enuresis    458 

Eosinophilia    163 

Ephemeral    Fever...- 1/3 

Epidemic   Disease    73 

Epiderm     and     Epithelium,     Re- 
generation  of    242 

Epilepsy    425.  428 

Epithelial    Cysts    4^5 

Exhaustion     40 

Exitus  Lethalis loi 

Exogenous   Pigmentation    215 

Exostoses  354 

Expectoration     453 

Experimental   Pathology   8 

External     Respiration 448 

Exudate    264 

Eye  in  Death 105 

F 

Fainting    424 

Falling    Sickness     425 

False  Membrane  274 

Fat  Embolism    150 

Fatty  Changes    192 

"      Degeneration     I93>  198 

Infiltration     192 

Faults  of  Heat  Regulation 165 

Fecal   Concretions    226 

Fever    ■ 165 

"        Production  of   168 

Stages    of 171 

Types  of    I70 

Fibrino-purulent  Exudate   278 

Fibrinous  Exudate   273 

Fibroblasts    ~37 

Fibroma    34i 

Durum    34i 

Growth  of    345 

Molle    342 

Fibromatosis     345 

Fistula    282 

Flatulence    439 

Food.   Deprivation   of 36 

Freezing    44 

Functional  Abnormalities     423 

"           Overstimulation     ....     40 
"          Pathological   Disturb- 
ances            4 


468 


Index. 


G  PAGE 

Galen     '•  . . , I2 

Gall  Stones   ^23 

"  "       Composition  of   ....   223 

Gangrene    181 

Gangrenous  Emphysema    183 

Gastric  Atony    439 

Gelatinous   Cancer    412 

General   Nervous   Disturbances..  423 

Pathology    5 

Germinal  Variation   32 

Giant    Cells    239 

"       Cell   Sarcoma    368 

Gigantism    3i>  254 

Glanders    '. 311 

'■         Abscesses    .• 315 

Bacillus  of   311 

Indurations    315 

•     '•  Nodules     314 

Ulcers     314 

Glands.   Regeneration   of 244 

Glandular   Cell   Cancers 406 

Glioma    360 

Retinal    361 

Glycogenic  Infiltration    205 

Glycosuria     456 

Gout     229 

Granulation   Tissue    ....241.   283.  285 

H 

Hemangioma    3^^ 

Ha;matemesis    122 

Hematocele    122 

Haematogenous   Pigmentation   .  ..  210 

Hsematoma     122 

Hematuria    122 

Hemic   Poisons    53 

Hemochromatosis     210 

Hemoglobinemia     160,  210 

Hemoglobinuria     160,  211 

Hemolysins    25 

Hemopericardium     122 

Hemoptysis    122 

Hemorrhage    119 

Results    of 124 

"  Symptoms    of 122 

"  Varieties   of    121 

Hemorrhagic  Anemia   158 

"  Infarct     I45 

"  Inflammation    ....   283 

Hemosiderin    211 

Hemothorax    ._ 122 

Haptophore    23 

Health,  Definition  of i 

Heart,  Condition  of,  in  Disease.    106 

Heat  Regulation,   Faults  of 165 

"      Stroke   41 

Hemiplegia     429 

Hereditary  Defects  of  Animals.  .     34 
"    Man    ....     33 


PAGE 

Heredity,  Atavistic   33 

Collateral     33 

Direct    33  ' 

Latent    33 

Heterotopic,     Heterochronic    and 

Heterometric  Processes   ......  3 

Hippocrates    1 1 

History    of    Pathology 10 

Hodgkin's  Disease   373 

Homogeneous  Thrombi    134 

Hoof,  Regeneration  of 243 

Host    of    a    Parasite 7? 

Humoral  Pathology  n 

Hyalin    Degeneration    199 

Hydremia    161 

Hydrocele    130 

Hydrocephalus    130 

Hydropericardium     130 

Hydrops    126 

Hydrothorax    130 

Hyperacidity     438 

Hyperemia     112 

Hyperesthesia     43^ 

Hypercholia    213 

Hyperchromatosis     209 

Hyperglycemia    45^ 

Hyperidrosis    463 

Hyperkinesis     427 

Hj'perleucocytosis    162 

Hypernephroma    393.  397 

Hyperthermia    41,  165 

Passive    166 

Hypertrophy    254 

I 

Icterus    212,  446 

Idiosyncrasy     20 

Ileus 444 

Immunity     16 

Acquired    21 

Active     28 

Natural    24 

Passive     28 

Relative    20 

Impotence     461 

Incubation,  Period  of 64 

Indirect    Symptoms    92 

Infarction    145 

Infection    54 

Embolic     05 

"         General    66 

Local     65 

Regional    65 

Infectious  Agencies   ■•  54 

"  Diseases      and      Their 

Agents,  Table  of   .  .  73 

Matter    55 

Inflammation    258 

"  Anatomical  Types  of  272 

Cardiac  Valves   272 


Index. 


469 


PAGE 
Inriainmation,  Cardinal  Symptoms 

of   260 

Causes  of   258 

Chronic    284 

Corneal    271 

Interstitial     285 

"  Nomenclature       and 

Classification    ....  288 

"             Phenomena    of    ....  260 

"             Productive    284 

Specific     286 

"             Suppurative    277 

"             Termination  of   ....  289 

Inflammatory  CEdema   128,  273 

Inherited  Diseases   30 

Insanity     426 

Intermittent   Disease    95 

Intestinal  Calculi   226 

Intestines,   Diseases  of 440 

"          Fermentation   in    ....  441 

Intoxication    50 

Intrauterine  Disease,  Origin  of.  .  31 

Intussusception    443 

Irritability,    Psychic 426 

Ischsemia     118 

Itching    432 

J 

Jaundice     212 

"          Sequels    to 214 

L 

Latent  Disease   97 

Leiomyoma    357 

Leucocytosis    162 

Leucopenia    162 

Leukaemia     163 

"Licking"     427 

Lightning  Stroke    48 

Lipoma    346 

Occurrence  of   348 

Liquefaction    Necrosis    181 

Liver,  Diseases  of    444 

"       Functions    of 445 

Local   Variations   in    Amount   of 

Blood    Ill 

Low  Temperatures.    Effects  of.  .  43 

Lungs,   Diseases   of 448 

Lymphangioma    364 

Lymphatic   Thrombosis    154 

Lymphatismus     27^ 

Lymphogenous   Embolism    154 

Lymphoma    ^,72 

M 

Malignant   Embolism    151 

Mania    426 


PAGE 

-Marasmus     190 

^Mechanical    Influences    49 

]\Ielanin    209 

Melanoma    2>77 

Melanosarcoma     377 

Melanosis     209 

Metabolism    in    Fever 173 

Metastasis    151 

jNIeteorism    439 

Methaemoglobin    160 

Metrorrhagia    122 

Miasmatic    Disease    71 

]\Iicrobes    54 

Microphytes    17 

Microzoa    17 

Miliary  Tubercle    300,  303 

Alineral    Poisons 51 

Miscarriage     162 

Miserere     444 

Mixed    Infection 69 

Thrombi     135 

Motor  Disturbances    427 

Automatic     .  427 
Coordinated     427 

Reflex     427 

Voluntary     .   427 

JMucoid  Degeneration    202 

Mummification    179 

Muscle,   Regeneration  of 245 

Myelogenous   Sarcoma    369 

Myoma    356 

Myositis   Ossificans   Progressiva.   355 

Myxcedema   460 

Myxoma    349 

Myxosarcoma     ....'. 369 

N 

Necrosis    176 

Causes  of  177 

Symptoms  of   183 

"          Terminations    of    184 

"          with    Coagulation 179 

"             "        Desiccation    ....  179 

Putrefaction    .  . .  181 

Softening    181 

Neoplasms     325 

Nerves,   Regeneration  of 248 

Nervous   Disturbances   423 

"           Hypertrophy   257 

Neuralgia    431 

Neurofibroma    359 

Neuroma     358 

"           Amputation     250,  358 

Neuromyxoma    359 

New  Growths    325 

Nosolog>^    5 

Nutrition,   Disturbances   of 36 

Nymphomania    426 


470 


Index. 


O  PAGE 

Obesity    197 

Obstruction  of  Intestines 443 

"     Blood    Vessels...  131 

Occluding    Thrombi    136 

Odontoblastoma     418 

Odontoma    418 

"           Durum    419 

"           Mixtum     419 

CEdema    126 

"        Results  of  130 

Oligsemia    157 

Oligocythsemia    157 

Oliguria    454 

Oncology    326 

Organization    of    Thrombi 138 

Osteoclasts    248 

Osteocystoma    420 

Osteoma    353 

"         Varieties  of    353 

Osteo-sarcoma     353 

Oxygen  Supply,  Deprivation  of..  38 

P 

Pain    431 

Palsy    429 

"      Results   of    430 

Pancreas,  Diseases  of 447 

Pandemic   Disease    72, 

Papilloma    383 

Paradoxical  Embolism   142 

Parsesthesia     432 

Paralysis     429 

Paralytic    Calf    Fever .  .  462 

Paraplegia     429 

Parasites    76 

Table   of    82 

Parasitic  Diseases   76 

Parenchymatous     Inflammation.  .  287 

"                  Poisons     53 

Passive    Congestion    115,  127 

"        Hypersemia     114 

"        Hyperthermia     166 

Pathogenesis     4 

Pathogenic  Microorganisms    ....  55 

Pathognomonic    Symptoms 92 

Pathognomy     5 

Pathological      Changes      of      the 

Blood    156 

Pathological     Processes,    Classes 

of    3 

Pathology    i 

"           History   of    10 

Periostoses    354 

Perithelioma    ■ 382 

Petechise 122 

Petrification    216 

Phagocytosis    18,  161 

Pharynx,  Diseases  of 437 

Phlegmon    282 

Pigmentation     209 

Pigmented  Tumor   t,-/~ 


PAGE 

Placental  Origin  of  Disease 30 

Plethora     157 

Poikilocytosis    159 

Poisons     50 

"         Classification  of   52 

Polychromatophilia     159 

Polymorphocellular    Sarcoma....  369 

Polyuria    454 

Post-mortem    Clots    132 

Precipitins    26 

Predisposition     16 

Pressure    Atrophy    187 

Primary  Lesion 98 

"         Thrombi     .  .'. 136 

Processes    of    Repair    and    New 

Formation     232 

Productive    Inflammation    284 

Prognosis    94 

Progressive   Inflammatory  Ostei- 

tosis     355 

Prophylaxis     5 

Protective  Substances    21 

Proud   Flesh    28^ 

Psammoina     382 

Psychical   Disturbances    424 

"          Excitement     426 

Ptyalism     436 

Pus    277 

Concretions     228 

Putrefaction   After  Death 105 

"  of    Exudate    283 

Putrid   Necrosis    181 

R 

Ray  Fungus   321 

Receptor    22 

Recovery   from   Disease 100 

Red   Thrombi    I35 

Regeneration    232 

"  Capacity   for    235 

"             of  Blood  and  Lymph  251 
"  Blood  Vessels  ...  240 
"  Bone     and     Car- 
tilage       246 

"              "  Connective    Tissue  237 
"  Corneal       Epithe- 
lium        243 

"              "  Epiderm  and  Epi- 
thelium        242 

"  "  Glands     244 

"  Hair    243 

"  "  Hornv     Tissue.  . .   243 

"  Muscle    245 

"  "  Nerves    2.18 

"  Tendon    Tissue.  .  246 

Remittent    Disease    95 

Resistance    to    Disease 16 

Respiration,    Disturbances   of....  448 

Respiratory   Faults    38 

Retrograde  Embolism 142 

Rhabdomyoma    356 


Index, 


471 


PAGE 

Riding   F.niliolus    I39 

Rigor    Mortis    104 

Round    Cell    Sarcoma 36/ 

S 

Sago    Spleen    208 

Salivary   Calculi    225 

Salivation    436 

Sapreniia    185 

Saprophytes    56 

Sarcoma     365 

Cells  of   •• 365 

Classes  of ..   366 

■'         Development    and   AiU- 

ology    of    371 

"         Gross    Appearances   of.   370 

Scars    Following   Infarction 147 

Scirrhus   Cancers    41 3 

Secondarv    Lesions    98 

"       '     Thrombi     136 

Secretory  Abnormalities 435 

Sensation,    Pathological    Diminu- 
tion of   43 ' 

Sensory  Disturbances    431 

Sequestration    178,  184 

Sero-fibrinous   Exudate   275 

Serous   Inflammation 273 

Exudate     273 

Sexual    Organs,    Diseases   of....   461 

Shock 50 

Side-chains     22 

Skin   Diseases    462 

Spasms    427 

Results  of   429 

Special    Pathology    5 

Spindle    Cell    Sarcoma 368 

Squamous   Epithelioma    404 

Starvation     36 

Stellate  Cell   Sarcoma 369 

Sterility    461 

Stomach,    Diseases    of 437 

Strangulation  of  Intestine 443 

Stratified    Thrombi    135 

Struma    Petrificans    2ig 

Sudden  Death    103 

Sufit'ocation 451 

Suffusion   of   Blood 122 

Suppuration    277 

Symptomatology     Qi 

Symptoms   of   Death 104 

Syncope    424 

T 

Tendon  Tissue.  Regeneration  of.  246 

Teratoma     4i5-  42t 

Terminations  of  Disease 99 

Therapeutics    94 

Therapy    5 

Thermic  Influences    41 

Thermometry    I75 

Thrombosis    131 


PAGE 

Thrombosis,    Causes    of 132 

Results    of    142 

Thyrt)i<l     Function,     Disturbances 

of    459 

Tissue    Immunity    63 

"       Predisposition     63 

Tonic   Spasms    428 

Toxalbumens    51 

Toxincs     51.     57 

Toxophore     23 

Transplantation    251 

Traumatic    Influences    49 

Trophic  Disturbances    434 

Tuberculin     310 

Tuberculosis     •  . .  ■   291 

"  Anatonn"cal     Lesions 

of   298 

Bacillus  of    292 

Heredity   of   295 

"  Mode  of  Contagion.   294 

Symptoms  of   310 

Tuberculous   Cavities    307 

"  Granuloma    305 

Ulcers    305 

Tumors    325 

.Etiology   of 3.V^ 

"  "  "  Cohnheim's 

Theory    .  .    3,Vi 

Classification  of 34° 

"         External    Shape    of -^28 

Growth   of    328 

"         Pathological    Signiticance 

of    329 

U 

Ubiquitous  Disease    72 

Ulcer 282 

UnderuMtrition     38 

Uniceptors     24 

Uraemia     459 

Urinarv   Calculi    220 

"    '    Gravel    220 

Organs,  Diseases  of....  454 
Urolithiasis     220 

V 

Valvular   Thrombi    136 

Vasomotor  Disturbances    435 

Vegetable   Poisons    5' 

Vertigo     424 

Vibices     122 

Virulence   of   Toxines 58,     59 

Vomiting    44° 

Vomitus    440 

W 

Wart    385 

Water,  Withdrawal  of 37 

White   Thrombi    135 

Work  Hypertrophy   254 


W.  T.  KEENER  &  COMPANY 

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text-book  of  comp-\rative  general  pathol- 
ogy for  the  use  of  practitioners  and 
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By  prof.  dr.  TH.  KITT.  of  MuincH. 

Auttorized  translation   from   the    German    by   Ds.    William    W.    Cadjbl'ky, 

Assistant  Demoijstrator  of  Pathplogy;  Edited  by  Dr.  Att.fn  J.  Smith, 

Professor    of    Pathology    in    the    University    of    Pennsylvania. 

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Kitt's  work  on  General  Pathology  is  the  only  especi-al  text- 
book on  Veterinarv-  Pathology  published.  Heretofore  students 
and  veterinarv-  surgeons  have  had  to  consult  works  on  human 
medicine  in  order  to  learn  the  foundations  of  pathology- ;  this  vol- 
ume, however,  is  ■wnritten  with  special  reference  to  the  student  of 
animal  medicine. 

After  an  introductory  review  of  the  general  conceptions  of 
disease  and  of  the  history  of  patholog}'.  the  causes  of  disease  are 
discussed:  then  pathologic  disturbances  under  four  main  headings. 
viz.:  (r)  Circulatory  Disorders;  (2)  Metabolic  Disorders,  Degen- 
erations and*  Necroses:  (3)  Reparatory  Processes  and  ProHfera- 
tion:  (4)  Functional  Disorders.  All  of  the  most  common  and 
characteristic  processes  are  illustrated  by  a  number  of  original 
drawings  and  colored  plates. 

The  style  of  the  book  is  terse  and  concise  and  all  the  defini- 
tions are  clear  cut:  the  work  is  thoroughly  up  to  date,  as  all  the 
results  of  the  recent  investigations  with  the  pathology  and  etiologv' 
of  disease  are  included  in  the  text  and  are  described  in  a  very 
simple  and  popular  manner.  The  practicing  veterinarian  will  find 
in  this  book  a  modem  work,  convenient  for  ready  reference,  and 
containing  evervi:hing  that  we  know  to-day  regarding  Veterinary 
Patholos^'. 


W.  T.  Keener  &  Co.^  CniCAGa 


SURGICAL  DISEASES  OF  THE  DOG  AND  CAT. 

With   Chapters  on   An?esthetics  and  Obstetrics. 

(Second  Edition  of  Canine  and   Feline   Surgery.) 

By  FREDERICK  T.  G.  HOBDAY,  R  R.  C.  V.  S.,  F.  R.  S.  E. 

Member  of  the  Board  of  Examiners  of  tlie  Royal  College  of  Veterinary 
Surgeons ;  Late  Professor  in  the  Royal  Veterinary  College,  London ; 
Consulting  Veterinary  Surgeon  to  the  British  Bulldog  and  Griffon 
Bruxellois  Clubs;  Honorary  Veterinary  Surgeon  to  the  Ladies'  Ken- 
nel  Association,   the    Fox-Terrier    Club,    etc. 

One    volume,    366    pages,    5^x8^    inches.-    With    241    illnstrations. 

Cloth,  $3.25  net. 


"The  reception  accorded  to  the  first  edition  has  proved  that 
a  small  text-book  of  the  kind  was  distinctly  wanted,  and  in  pre- 
senting a  second  and  enlarged  edition  the  author  regrets  that 
illness  and  other  causes  have  allowed  the  first  to  remain  so  long 
out  of  print. 

By  the  request  of  numerous  friends,  the  work  has  been  en- 
larged to  include  symptoms  and  general  details  of  treatment  other 
than  that  which  may  be  described  as  purely  surgical,  although  the 
original  idea  of  the  author  to  keep  the  book  as  a  handy  manual  for 
their  final-year  student  has  still  been  adhered  to. 

The  introduction  of  antiseptics  has  revolutionized  all  of  the 
old-fashioned  ideas,  and  has  benefited  the  animal  world  to  almost 
as  great  an  extent  as  that  of  man. 

It  is  true  that  we  have  not  quite  the  same  advantages  as  our 
confreres  in  human  surgical  practice,  but  it  is  astonishing  what 
can  be  done  by  strict  attention  to  the  principles  introduced  by  the 
discoveries  of  Pasteur,  and  applied  to  surgery  by  the  teachings  of 
Lister. 

Operations  which  only  a  few  years  ago  were  looked  upon 
beforehand  with  dread  are  now  done  every  day,  and  owners  of  pet 
animals  have  learned  to  appreciate  the  value  of  modern  antiseptic 
methods  almost  as  much  as  the  members  of  the  profession  them- 
selves."— Extract  from  Preface. 


W.  T.  Keener  &  Co.,  Chicago. 


SPECIMEN    PAGE. 


OPERATIONS  ON  THE  MOUTH,  PHARYNX,  ETC.       133 

After-treatment  consists  merely  in  the  application  of  a 
little  antiseptic  lotion  (boric  acid,  chinosol,  or  permanganate 
of  potash)  several  times  a  day. 

Sarcoma  or  Carcinoma — Symptoms. — As  a  general  rule 
the  first  signs  will  merely  be  a  capricious  appetite  and  diffi- 
culty in  swallowing,  the  animal  appearing  to  have  a  very  sore 
throat.     There  is  salivation,  and,  after  the  trouble  has  existed 


-7=!€^^ 


Fig.  102.  —  Carcinoma  of  the 
Pharynx  and  Cervical  Glands 
of  a  Terrier. 


Fig.  103.  —  Endothelioma  per- 
forating the  Palate  of  a  Creat 
Dane. 


for  a  few  weeks,  a  gradual  emaciation  of  the  body  will  be 
observed.  It  is  not  uncommon  upon  discovering  a  sore  at 
the  back  of  the  mouth,  such  as  is  illustrated  in  Fig.  102,  for  a 
diagnosis  to  be  made  of  an  injury  from  a  sharp  bone  or  a 
piece  of  stick.  This  had  been  actually  done  in  each  of  the 
cases  from  which  Figs.  102  and  103  were  sketched.  All  doubt 
on  this  question  can  be  set  aside  if  the  wound  has  a  ragged, 
ulcerated  appearance,  shows  no  tendency  to  heal  after  careful 


AN  UNIVERSAL  STANDARD. 


FRIEDBERGER    &    FROHNER'S 
VETERINARY    PATHOLOGY. 

(Authorized   Translation) 

Bv  M.  H.  HAYES,  F.  R.  C.  V.  S. 
Author  of  "Points  of  the   Horse,"  "Veterinary  Notes  for  Horse  Owners,"  etc. 

Edited  by  JOHN  DUNSTAN,   M.  R.   C.  V.  S. 

Professor    of    Surgery    and    Therapeutics    at    the    Royal     (Dick)    Veterinary 

College,   Edinburgh. 


There  has  long  been  wanting  in  Veterinary  Hterature  a  com- 
prehensive text-book  deaHng  with  the  Diseases  of  Animals  from 
their  clinical,  pathological  and  therapeutic  standpoints  and  which 
might  have  some  claim  to  the  term  "modern."  This  gap  was  effi- 
cientl}-  filled  in  Germany  by  P'riedberger  and  Frohner's  splendid 
production,  the  value  of  which  was  soon  correctly  estimated  by 
veterinary  surgeons  of  all  nations. 

The  late  Captain  Hayes,  the  most  prolific  English  veterinary 
writer  of  modern  times  and  editor  of  many  valuable  works  on 
veterinary  and  equine  matters,  ever  quick  to  appreciate  merit, 
bought  the  right  to  translate  the  work  into  English.  Two  editions 
of  the  first  volimie  were  published  during  his  life,  and  he  was 
engaged  on  the  translation  of  the  second  volume  at  the  time  of  his 
^eath.  Dr.  Dunstan  was  requested  by  ]\Irs.  Hayes  to  complete 
this  volume.  The  work  has  also  been  translated  into  French  and 
Russian  and  is  the  recognized  text-book  in  American  and  Euro- 
pean Veterinary  Colleges. 

Two  volumes,   8vo.      1,285   pages.      Cloth.      Price   per   set,   $8.00  net. 


CONTENTS. 


VOLUME    I. 


Chapter  I,  Infective  Diseases;  II,  Miscellaneous  Infective  Diseases;  III, 
Chronic  Constitutional  Diseases ;  IV,  Addenda  to  Infective  Diseases ; 
V,   Notes   on   Bacteriology;    VI,   The   Terms   Infection   and    Contagium. 


VOLUME    11. 


Chapter  1,  Diseases  of  the  Organs  of  Digestion;  II,  Diseases  of  the 
Esophagus;  III,  Diseases  of  the  Stomach;  IV,  Diseases  of  the  Liver; 
V,  Diseases  of  the  Peritoneum;  VI.  Diseases  of  the  Spleen;  VII, 
Diseases  of  the  Urinary  Organs ;  VIII,  Diseases  of  the  Sexual 
Organs;  IX,  Diseases  of  the  Heart  and  Larger  Blood  Vessels  ;^  X, 
Skin  Diseases;  XL  Diseases  of  the  Locomotory  Organs;  XII,  Trichi- 
nosis in  Swine;  XIII,  The  Measles  of  Domestic  Animals;  XIV, 
Miescher's  Tubes  or  Rainey's  Corpuscles;  XV.  Diseases  of  the  Nervous 
System;  XVI,  Diseases  of  the  Spinal  Cord  and  of  Its  Membranes; 
XVII,  Diseases  of  the  Peripheral  Nerves;  XVIII,  Neurosis  without 
Known  Anatomical  Basis;  XIX.  Appendix  to  Diseases  of  the  Nervous 
System;  XX,  Diseases  of  the  Respiratory  System;  XXI,  Diseases  of 
the  Accessory  Cavities  of  the  Nose;  XXII.  Diseases  of  the  Larynx; 
XXIII.  Diseases  of  the  Trachea  and  Bronchi;  XXIV,  Diseases  of  the 
Lungs;  XXV,  Diseases  of  the  Pleura;  XXVI,  Appendix  to  Diseases 
of  the  Respiratory  Organs. 


OPINIONS  OF  FRIEDBERGER  &  FROHNER. 

"It  is  this  work  tliat  I  recommend  to  my  students,  and  believe  that  of  all 
works  on  Veterinary  Medicine,  it  is  the  best  adapted  to  class  room  use."— 
Leonard  Pearson.  Dean  and  Professor  of  Practice  Veterinary  Medicine,  De- 
partment of  Veterinary  Medicine,  TTniversity  of  Pennsylvania. 

"Hope  you  will  be  amply  repaid  for  its  production— this,  the  most  modern 
and  bes't  text-book  we  have."— J.  L.  Robertson.  Professor  of  Veterinary  Medi- 
cine.  New  York  Veterinary  College. 

"I  take  pleasure  in  making  a  very  favorable  report,  after  a  careful  review, 
on  Veterinary .  Pathology  bv  Friedberger  and  Frohner,  translated  by  M.  H. 
Hayes,  F.  R.  C.  V.  S.,  and  consider  it  the  best  work  to-day  on  theory  and 
practice  of  Veterinary  Medicinp  for  stud^Mts'  use,  and  have  recommended  it  to 
the  students  of  the   Chicago  Veterinarv  College." 

(Signed)  A.   H.   B.\KER.  V.  S.. 

Dean 'of  Faculty  and  Professor  of  Theory  and  Practice. 

"I  find  that  the  print  is  excellent,  that  the  tmnslator  has  put  the  t'-chnioal 
statements  into  free  and  easily  understood  English  language,  making  the  text 
easily  comprehended  by  the  .average  student.  You  will  note  by  the  catalogue 
mailed  you  this  day  this  work  has  been  adopted  as  the  text-book  of  this 
college."— S.  Stewart.  M.  D.,  D.  V.  S.,  Professor  of  Veterinary  Medicine.  Kaii,sis 
City  Veterinary  College. 

"For  many  years  Friedberger  and  Frohner's  'Lehrbuch  der  Speciellen 
Pathologie  und  Therapie  der  Hausthiere'  has  been  considered  by  competent 
.iudges  to  be  the  best  treatise  on  diseases  of  animals  and  their  treatment.  It 
is  not  alone  of  inestimable  value  to  the  practitioner,  but  it  must  be  regarded  as 
an  important  addition  to  medical  literature,  fo  which  the  research  scholar 
gladly  turns.  The  work  has  already  been  translated  into  French  and  Russian, 
and  is  used  as  a  text-book  in  those  countries.  An  English  translation  should, 
therefore,  be  hailed  with  delight,  as  there  is  no  really  good  English  work 
covering  the  Practice  of  Veterinary  Medicine." — Boston  Medical  and  Surgical 
Journal. 
M  Ordering  FRIEDBERGER  and  FROHNER  to  ensure  latest  edition  specify  Hayes'  Translation. 


W.  T.  Keener  &  Co.,  Chicago. 


Tiie  only  strictly  up-to-date  Veterinary  Physiology  in  the  English  language. 

ESSENTIALS    OF    PHYSIOLOGY    FOR 
VETERINARY    STUDENTS 

By   D.   NOEL  PATON.   M.   D.,   B.   Sc,  F.   R.   C.   P.,   Ed. 

Superintendent  of  Research  Laboratory  of  the  Roj-al  College  of  Physicians 
of  Edinburgh ;  Lecturer  on  Physiology,  School  of  Medicine  of  the 
Royal  College,  Edinburgh :  Examiner  in  Physiology  in  the  University 
of  Glasgow  and  for  the  Royal  College  of  Physicians,  Edinburgh,  and 
late  Examiner  in  the  L^niversity  of  Edinburgh  ;  Examiner  in  Physiology 
for  the  Royal  College  of  Veterinary  Surgeons ;  Late  Professor  of 
Physiolog}',    Royal   Dick    Veterinary    College,    Edinburgh. 

One   volume.    428   pages,    5^x8^    inches.      Profusely    illustrated. 

Cloth,   $3.00   net. 

Between  the  Physiology  of  man  and  that  of  domestic  animals 
there  is  no  fundamental  difference  and  most  of  our  knowledge  of 
human  physiology  has  been  acquired  from  experiments  tipoii  the 
lower  animals.  Btit  while  the  tissues  of  a  man.  a  dog  and  a  horse 
act  mttch  in  the  same  manner,  the  mode  of  ntitrition  of  these  tis- 
sues is  somewhat  dift'erei>t  and  rec[uires  special  attention  in  the 
case  of  each. 

In  this  volume  the  attempt  is  made  to  give  the  Essentials  of 
General  Physiology  and  of  the  special  physiology  of  the  domestic 
animals   in  a    form  suitable  to   the   requirements   of   students  and  . 
practitioners  of  veterinary  medicine. 

OPINION. 

"The  examination  which  we  have  been  able  to  give  this  work 
has  left  a  ver\-  favorable  impression,  as  it  appears  that  the  essen- 
tials have  been  included,  with  nothing  omitted  except  the  padding, 
which  in  some  text-books  of  physiology  reqtiire  a  vast  amount  of 
reading  to  extract  them,  resulting  in  much  confusion  to  students 
and  those  who  do  not  have  the  time  nor  inclination  to  make  the 
search  for  facts. 

"We  recommend  the  work  heartily  in  the  sense  that  it  reduces 
the  study  of  physiology  to  a  'reasonable'  basis,  and  the  atithor  has 
done  for  the  reader  what  is  a  difficult  task  upon  his  own  account. 
Well  printed,  well  bound,  intelligently  illustrated,  ]\Iessrs.  Keener 
have  placed  a  'reasonable"  physiology  before  the  profession  at  a 
reasonable  price." — Am.   Vet.  Reviezv. 

W.  T.  Keener  &  Co.,  Chicago. 


specimen    Page    of   Patau's    Veterinary    Physiology. 


THE  FOOD  AND  DIGESTION 


307 


up  and  prepared  for  digestion.     In  the  horse  the  lips  are 

long  and  prehensile,  and  are  essential  for  the  taking  of  food. 

Into    the    mouth   three    pairs    of    compound    glands — the 

Salivary  Glands — open.     The 

parotid,     lined     entirely      by 

enzyme-secreting    epithelium, 

opens    on    the    side    of    the 

cheek,  while  the  submaxillary 

gland,  composed  partly  of  acini 

with    enzyme  -  secreting,    and 

partly  of   acini   with    mucin- 

secreting  epithelium,  and  the 

sub-lingual,  composed  entirely 

of  mucin-secreting  acini,  open 

under  the  tongue  (S.G.). 

The  tongue  in  the  horse  is 
smooth,  but  in  the  ox,  and 
especially  in  the  cat,  it  is 
covered  with  a  fine  fur  of 
processes,  the  filiform  papilla, 
which  are  of  use  in  passing 
the  food  backwards  along  its 
surface  in  the  act  of  swalloAv- 
ing.  (For  Organs  of  Taste  see 
p.  132.) 

Posteriorly,  the  mouth  opens 
into  the  pharynx  (Ph.)  or  upper 
part  of  the  gullet.  In  the 
horse  the  soft  palate  is  very 
long,  reaching  to  the  base 
of  the  epiglottis,  and,  unless 
during  swallowing,  shutting  oft 
the  mouth  from  the  pharynx 
(Fig.  137).  On  each  side, 
between  the   mouth   and    the 

pharynx,  is  the  tonsil  (T.),  an  almond-Hke  mass  of  lymphoid 
tissue.  The  pharynx  is  a  cavity  which  can  be  shut  off 
above  from  the  posterior  nares  by  raising  the  soft  palate, 
and  by  pulling  forward  the  posterior  pharyngeal  wall.  It  is 
surrounded  by  three  constrictor  muscles,  which,  by  contracting 


Pig.  138. — Diagram  of  the  Parts  of 
the  Alimentary  Canal,  from  Mouth 
to.  Anus.  T.,  Tonsils;  Ph., 
Pharynx;  S.C.,  Salivary  Glands; 
Oc,  CEsophagus ;  C,  Cardiac; 
Py.,  Pyloric  Portion  of  Stomach  ; 
i). ,  Duodenum;  Li.,  Liver;  P., 
Pancreas  ;  ./■.,  Jejunum;  /.,  Ileum  ; 
v.,  Vermiform  Appendix;  Col., 
Colon ;  li.,  Rectum, 


ANNOUNCEMENT 


PATHOLOGY 


OF 


METABOLISM 


Edited  by 

CARL   VON    NOORDEN 

FIRST  MEDICAL  CLINIC,  VIENNA.    LATE  OF  FRANKFORT. 


Contributions  by 


ADALBERT  CZERNY  iBreslam,  CARL  DAPPER  (Kissingem, 
FR.  KRAUS  (Berlin  I,  OTTO  LOWEI  (Viennai,  ADOLF 
MAGNUS-LEVY  (Berlin),  M.  MATTHES  iColognei,  LEO 
MORH  (Berlin),  CARL  NEUBERG  (Berlin),  HUGO  SALOMON 
(Frankfort,  AD.  SCHMIDT  (Dresden),  FRANZ  STEINITZ 
(Breslaui,  H.  STRAUSS  (Berlin  i,  W.  WEINTRAUD  (Wiesbaden). 


SECOND  EDITION 
Authorized  English  Translation.      Edited  with  Additions. 

By 

I.  \VALKER   HALL,  M.  D. 

Professor  of  Pathology,  University  College,  Bristol. 


THREE  VOLUMES,  8vo.  -  -  CLOTH,     $16.00 

Payable,  $4.00  on  receipt  of  Volume  One;    $6.00  on  receipt 
of  Volume  Two   and   $6.00   on   receipt   of  Volume   Three 


W.  T.  KEENER  &  CO.,  CHICAGO 
1906 


# 


PREFACE  TO  THE_ENGLISH  EDITION. 

An  Ensflish  Edition  of  von  Xoorden's  well-known  "Lehrbuch 
Stoffwechsel"  does  not  require  any  sf)ecific  introduction. 

Although  the  arrangement  of  the  sections  and  their  contents  is 
the  same  as  that  of  the  first  edition,  the  present  text  is  mainly  due 
to  the  co-operation  of  a  number  of  workers  in  this  branch  of 
Medical  Science.  In  his  preface  to  the  first  German  Edition, 
von  Noorden  acknowledged  the  encouragement  and  assistance  of 
Gerhardt,  von  Jurgensen  and  Riegel ;  in  his  introduction  ^o  the 
second  edition,  he  expresses  his  grateful  thanks  to  the  collabora- 
tors, ''whose  unflagging  and  zealous  work  alone  has  made  it  possi- 
ble to  bring  out.  instead  of  a  second  edition  of  my  text-book,  a 
hand-book  of  the  pathology  of  metabolism"  worthy  of  the  extent 
and  importance  of  the  subject. 

The  length  and  style  of  the  German  original  has  restricted  the 
addition  of  the  more  recent  work  in  detail.  The  additions  made 
to  both  the  text  and  bibliography  have  conformed  to  the  general 
principle  of  the  work  in  presenting  a  compilation  of  facts  and  a 
critical  discussion  of  hypothesis  rather  than  the  enunciation  of 
theories  ;  they  have  also  been  selected  in  harmony  with  the  view 
of  von  Noorden  and  others,  that  experiments  upon  animals  should 
be  cited  only  in  connection  with  acute  conditions ;  as  it  is  so  difficult 
to  compare  them  with  the  conditions  which  obtain  in  the  chronic 
diseases  of  human  beings,  these  addenda  have  been  incorporated 
in  the  text. 

It  is  a  pleasure  to  express  my  thanks  to  my  colleagues  for 
their  translations,  to  iny  friend  Professor  T.  H.  ]\Iilroy,  for  the 
many  valuable  suggestions  and  to  the  University  College  Demon- 
strator in  Pathology,  Dr.  Carey  Coombs,  for  his  careful  prepara- 
tion of  the  indices. 


CONTENTS    OF   THE    VOLU^IES. 

Volume   I. 

The    Physiology   of   Metabolism. 

By  ADOLPH  MAGNUS 'LEVY. 

Volume  II. 

Subject.  Author.  Translator. 

Hunger   and    Chronic   Inanition.  .  v.    Noorden    A.   Jex    Blake,    ]M.  D. 

Over    Feeding     v.    Noorden    R.  W.  Marsden,  ]\I.  D. 


Subject.                                     Author.  Translator. 
Fever    and    Infection F.    Kraus    J.    O.    Wakelin    Bar- 
rett, D.  Sc.  M.  D. 
Stomach     and     Intestinal     Dis- 
eases      Ad.     Schmidt     H.   French,  M.  D.,  F. 

R.  C.  P. 

Liver    Diseases     W.    Weintraud    R.  W.  Webster,  M.  D. 

Respiratory      and       Circulator}' 

Diseases      M'.    Matthes     A.   Jex   Blake,    M.  D. 

Blood    Diseases     H.    Strauss     J.   A.   Milroy,   M.   A., 

M.    D. 
Renal  -  Diseases    , .  v.    Noorden    C.   Edgeworth,  M.  D. 

Volume   III. 

Subject.  Author.  Translator. 

Diabetes      Carl    von    Noorden .  .  H.     French,     ^I.     D., 

F.  R.  C.   F. 

Obesity      Carl    von    Noorden .  .  D.    Spence,    Ph.    D. 

Gout      Carl    von    Noorden .  .  ,R.  ^^^  Webster.  M'.  D. 

Diabetes      Insipidus      and      Addi- 
son's    Disease     Leo    Mohr    T.   J.   Horder,   M.   D. 

Thyroid    Gland     A.    ]\Iagnus    Levy    .  .  A.   Jex    Blake,    M.  D. 

Carbohydraturia      Carl     Neuberg     J.  Dixon  Mann,  M.  D. 

F.   R.   C.    P. 

Cystinuria 

Alcaptonuria,      Oxaluria,       Phos- 

phaturia     Carl     Neuberg     W.     H.     Hurtley,    D. 

Sc. 

Nervous    System    

Muscles      Leo    Mohr    A.    Edwards    

Bones     

Cancerous    Affections     Adolf    Schmidt     ....  W.    Cramer,    Ph.    D. 

Skin    Diseases     Salomen     and 

von    Noorden    ....  J.    A.    Nixon,    ]\I.    B. 

Childhood      Czerny    and 

Steinitz      J.     Fortescue     Brick- 
dale,  M'.  D. 

Influence  of  Drugs   and   Poisons.  Otto     Lowei     J.     Fortescue     Brick- 
dale,  M.   D. 

Bath     and     Climate Matthes      J.    A.    Nixon,    'M.    B. 

Phototherapeutics     H.    Salomen     A.    Edwards. 


Volume   I   will   be   pulilished   in   the   late   autumn   of   1906.     Volumes    II 
and  III  in   1907. 


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